Grippal With Pseudoephedrine And Dextromethorphan 16 Capsules

Grippal With Pseudoephedrine And Dextromethorphan 16 Capsules

Paracetamol / Pseudoephedrine hydrochloride/ Dextromethorphan hydrobromide/ Chlorphenamine maleate

ACTION AND MECHANISM

- Combination of a [ANALGESIC] [ANTIPIRETIC], a [HISTAMINERGIC ANTAGONIST (H-1)], a central [ANTITUSSIVE] and a [NASO/PHARYNGEAL DECONGESTANT]. Paracetamol exerts analgesic and antipyretic effects, probably due to the inhibition of central prostaglandin synthesis. For its part, pseudoephedrine is an alpha-1 adrenergic agonist, which causes vasoconstriction, reducing nasal congestion. Dextromethorphan produces depression of the cough center. Finally, chlorphenamine antagonizes H1 and cholinergic receptors, eliminating cold symptoms such as sneezing, whining or runny nose.

INDICATIONS

- Symptomatic treatment of [COMMON COLD] and [FLU] that present with fever, moderate pain, headache, unproductive cough and runny nose.

POSOLOGY

- Adults: 1 capsule/6 to 8 hours as needed. The maximum daily dose is 4 capsules/24 hours.

- Children < 12 years: the safety and efficacy of this medicine have not been evaluated.

DOSAGE IN RENAL FAILURE

- Mild to moderate renal impairment (CLcr 50-90 ml/min): no dose adjustment is required.

- Severe renal insufficiency

* CLcr 10-50 ml/min: 1 capsule/6h

* CLcr < 10 ml/min: 1 capsule/8h

DOSAGE IN LIVER FAILURE

Do not exceed 2 g /24h. The minimum interval between doses will be 8 hours.

RULES FOR CORRECT ADMINISTRATION

The capsules should be swallowed whole with a glass of water. The administration of this medication should be started when the first symptoms appear. As these disappear, this medication should be discontinued.

CONTRAINDICATIONS

- Hypersensitivity to any component of the medication, including cases of [ALLERGY TO PARACETAMOL] or [ALLERGY TO OPIOIDS].

- [HEPATIC DISEASE], such as severe [LIVER FAILURE] or [HEPATITIS]. Paracetamol can lead to hepatotoxicity.

- [HYPERTHYROIDISM]

- [GLAUCOMA]

- [PORFYRIA]. H1-antihistamines are not considered safe in these patients.

- Heart disease/severe hypertension or uncontrolled diabetes mellitus. There is a risk of serious decompensation.

- [TOS] asthmatic and productive type

- Patients undergoing treatments with:

* MAOI-type antidepressants in the 14 days before starting therapy with pseudoephedrine or dextromethorphan (See Interactions).

*Serotonin reuptake inhibitor (SSRI) antidepressants

* Bupropion

* Linezolid

* Procarbazine

* Selegiline

- First trimester of pregnancy due to its pseudoephedrine content

PRECAUTIONS

- [RENAL INSUFFICIENCY]. Patients treated with high doses for long periods of time could experience renal adverse reactions, so it is recommended to monitor renal functionality. Patients with end-stage renal failure (CLcr < 10 ml/min) should be separated by at least 8 h. No special problems are expected in case of occasional use.

- [HEPATOTOXICITY]. During the hepatic metabolism of paracetamol, hepatotoxic compounds such as N-acetyl-benzoquinone imine are generated. This compound is produced in small amounts through metabolism by cytochrome P450, a minor pathway for paracetamol. However, at high doses of paracetamol, saturation of the fundamental pathways (glucuronide and sulfate conjugation) can occur, increasing the role of this cytochrome, and the consequent production of benzoquinone. This substance is rapidly detoxified with reduced glutathione expenditure, transforming into cysteine ​​and mercapturic acid, which is eliminated in the urine. If benzoquinone production is excessive, glutathione depletion occurs in the hepatocyte, and consequent cell damage, which could lead to life-threatening toxicity.

In general, self-medication should be limited, and paracetamol should not be used for more than 10 days without medical advice, and as long as the symptoms that motivated its use persist. Likewise, it is not advisable to exceed the recommended daily doses of 4 g in adults or 60 mg/kg in children.

Due to its hepatotoxic effects, and taking into account its indications and the alternative of other analgesics and antipyretics, as a general rule it is recommended to avoid its use in patients with liver disease, including [LIVER FAILURE], [HEPATITIS] or [LIVER CIRRHOSIS], as well as in patients with other risks of liver damage, such as [CHRONIC ALCOHOLISM], [HYPOVOLEMIA], [DEHYDRATION] or [ MALNUTRITION] with low glutathione levels, or treated with other hepatotoxic drugs.

In those patients in whom this is not possible, it is suggested to use it under medical criteria, after a careful evaluation of the benefit/risk ratio. It is recommended to evaluate liver function in these patients at the beginning of treatment and periodically throughout it. Likewise, the maximum doses to be used should not exceed 2 g/24 h (po) or 3 g/24 h (iv).

- Allergy to salicylates: Patients allergic to acetylsalicylic acid do not usually present cross hypersensitivity reactions with paracetamol. However, cases of mild bronchospasm have been reported in patients allergic to acetylsalicylic acid treated with paracetamol.

- [BLOOD DISCRASIAS]. Paracetamol has been related to hematological alterations such as [LEUCOPENIA], agranulocytosis or [NEUTROPENIA]. In the case of prolonged treatments, it may be necessary to perform periodic blood counts.

- Determination of pancreatic functionality. Paracetamol may interfere with the bentiromide test, since it is metabolized to arylamine, giving rise to a false increase in para-aminobenzoic acid. It is recommended to stop treatment with paracetamol at least three days before the test.

- It is recommended to evaluate the administration of this drug in patients with [HEPATIC FAILURE], [ASTHMA], [GLAUCOMA], bladder neck obstruction, pyloroduodenal obstruction, stenosing [PEPTIC ULCERA], symptomatic prostatic hypertrophy or urinary retention (the anticholinergic effects of chlorpheniramine can precipitate or aggravate it).

- It is recommended to evaluate the clinical situation before administering the medication in patients allergic to other antihistamines, since cross-sensitivity may occur.

- This medicine can produce [SEDATION]. Due to the risk of CNS depression, the patient should be advised to avoid the consumption of alcoholic beverages or the ingestion of CNS depressants (barbiturates or tranquilizers, MAOIs) together with this medication.

- Elderly patients may be more susceptible to the anticholinergic effects produced by antihistamines, such as: [DIZZENESS], sedation, [CONFUSION], [HYPOTENSION], [DRY MOUTH].

- Cough. It should not be used in case of chronic cough or cough due to smoking, since it can impair expectoration and increase the resistance of the respiratory tract.

- Atopic processes. It could worsen the symptoms of diseases such as [ATOPIC DERMATITIS] or [MASTOCYTOSIS] due to the increase in the release of histamine.

- [DRUG DEPENDENCE]. Dextromethorphan can potentially give rise to dependency phenomena (cases of abuse in adolescents have been described, sometimes leading to fatal poisoning), although to a much lesser extent than other opioids such as morphine. It is recommended to take extreme precautions and monitor the patient, especially people with a history of drug addiction, in case symptoms of abuse appear, such as mood swings, changes in the person's habits or appearance, abuse of large amounts of cough products or the disappearance of medicines from the home medicine cabinet.

- Neurological diseases. Assess the benefit/risk ratio in patients with neurological disorders associated with a decreased cough reflex, such as [Stroke], [DEMENTIA] or [PARKINSON'S DISEASE].

- Slow metabolizers. Dextromethorphan is a CYP2D6 substrate. About 10% of the general population is a poor metabolizer of this isoenzyme, with a risk of dextromethorphan accumulation and toxicity. Lower doses of dextromethorphan may be required.

- Limitations in clinical experience. Its efficacy and safety in patients with [KIDNEY FAILURE] or [HEPATIC FAILURE] have not been evaluated. Use with caution, especially in seriously ill patients.

- Patients in whom the sympathetic stimulation could worsen their pathologies, such as those with [diabetes], [glaucoma], [coronary insufficiency], [ischemic heart disease], [cardiac arrhythmia], [arterial hypertension], [hyperthyroidism], [pelocromocytoma], [anemia] or [prostatic hyperplasia]. The use of pseudoephedrine or any other sympathomimetic could aggravate the symptoms of these diseases, so its use without a prescription is not recommended. In the case of serious conditions, such as decompensated diabetes or severe heart disease, it may be advisable to avoid the administration of pseudoephedrine (See Contraindications).

- Patients with [INTESTINAL OBSTRUCTION] should not use prolonged-release oral forms without consulting a doctor.

- Caution should be exercised in patients receiving digitalis or being treated with ergotamine-type vasoconstrictors.

- The benefit/risk ratio should be carefully evaluated in the following situations: severe [LIVER FAILURE] or moderate to severe [KIDNEY FAILURE], [PROSTATIC HYPERPLASIA], positive history of [BRONCHIAL SPASM], stenosing [PEPTIC ULCER], pylorus-duodenal obstruction, history of [EPILEPSY].

- As with other CNS stimulants, pseudoephedrine carries a risk of abuse. Its administration at increasing doses can produce long-term toxicity. Its continued use may lead to tolerance, which could lead to an increased risk of overdose. Depression may occur after rapid withdrawal of pseudoephedrine treatment.

- At therapeutic doses, no clinically significant interaction with alcohol has been shown (for a blood alcohol level of 0.5 g/l). However, caution is advised if alcohol is taken concomitantly.

ADVICE TO THE PATIENT

- It is advisable to drink plenty of water during treatment, avoiding alcoholic beverages as much as possible.
- The doctor should be notified of any change in the patient's behavior or mood.
- It is recommended not to exceed the recommended daily doses and avoid treatments longer than ten days without a prescription.
- If the symptoms continue or worsen after five days, it is recommended to consult a doctor.
- The doctor or pharmacist should be notified of any disease the patient has or any medication they are taking, especially in the case of antidepressants.
- It can cause drowsiness, so caution is recommended when driving, and do not combine it with drugs or other sedative substances such as alcohol.

SPECIAL WARNINGS

- It is recommended to monitor the patient in case signs of abuse appear.

- In patients treated with anticoagulants, it is recommended to follow short treatments with low doses, controlling coagulation parameters.

- The association between products with dextromethorphan and antidepressants should be avoided, leaving at least 14 days of rest between the administration of both drugs.

- It is recommended to perform blood counts in patients treated with high doses or for prolonged periods of time.

- It is recommended to stop treatment at least 24 hours before surgery.

- It is advisable to control the levels of transaminases in patients with prolonged treatments or in danger of presenting hepatotoxicity.

- In case of overdose, the specific antidote for paracetamol is N-acetylcysteine.

INTERACTIONS

"INTERACTIONS RELATED WITH PARACETAMOL"

In general, interactions with acetaminophen are not expected to be serious, due to its occasional use. Only in those patients treated with high doses, especially if there are other risk factors for hepatotoxicity, or in long-term treatments, it is expected that interactions have clinical significance.

- NSAID. Paracetamol is usually used in combination with other analgesics, such as ibuprofen, for the treatment of febrile processes in children. However, it must be taken into account that its administration together with NSAIDs or salicylates at high doses and for prolonged periods of time could increase the risk of kidney damage. It is therefore recommended not to exceed the recommended doses and to limit joint treatment to the essential minimum.

- Oral anticoagulants. Contrary to what occurs with NSAIDs and acetylsalicylic acid, paracetamol does not have antiplatelet activity nor does it affect blood coagulation per se, which is why it is used as the analgesic drug of choice in patients treated with oral anticoagulants.

However, in the case of prolonged treatments and high doses, but without entering into toxic doses, a slight hepatotoxic effect could be produced, characterized by the decrease in the production of hepatic coagulation factors, so the INR of these patients could be increased, with risk of bleeding.

Therefore, it is recommended to monitor this parameter in these patients treated with high doses. The risk seems insignificant in the case of punctual treatments or in prolonged treatments with doses < 2 g/24 h.

- Busulfan. Risk of toxicity from busulfan, as paracetamol reduces glutathione levels, a substance with which busulfan conjugates when it is eliminated. It is recommended to avoid the administration of paracetamol, or limit exposure if this is not possible, in the 72 hours before and during treatment with busulfan.

- Chloramphenicol. Paracetamol could favor the accumulation of chloramphenicol by decreasing its hepatic metabolism, with the risk of haematological toxicity. It is advisable to monitor the patient.

- Drugs that delay gastric emptying, such as anticholinergics or exenatide. This delay could slow down the absorption of paracetamol and the onset of the effect, rather than its intensity.

- Hepatotoxic drugs. Paracetamol at high doses exerts a hepatotoxic effect. It is recommended to avoid its joint administration with other hepatotoxic drugs, as well as with alcohol.

- Enzyme inducers (estrogenic oral contraceptives, barbiturates, carbamazepine, phenytoin, rifampicin). Paracetamol is partially metabolized by cytochrome P450, so its plasma levels and therapeutic effects could be reduced in case of administration together with a drug that potently induces the hepatic microsomal system. On the other hand, in case of paracetamol overdose, the inducer could increase liver toxicity as a consequence of a greater production of toxic metabolites generated by this enzymatic system.

- Enzyme inhibitors (imatinib, isoniazid, propranolol). Increases in paracetamol plasma levels have been reported by drugs with inhibitory activity on its metabolism.

- Reverse transcriptase inhibitors (didanosine, zidovudine). Paracetamol could potentiate the haematological toxicity of zidovudine. On the other hand, both didanosine and zidovudine could favor acetaminophen hepatotoxicity.

- Lamotrigine. Paracetamol could increase the metabolism of lamotrigine, reducing its therapeutic effects.

- Ion exchange resins (cholestyramine, colestipol). Possible decreased absorption of paracetamol. Distancing the administration one hour.

The studies carried out have verified the absence of significant pharmacokinetic interaction with adefovir, amantadine, H2 antihistamines or proton pump inhibitors, argatroban, chloroquine, erythromycin, lithium, methotrexate, oseltamivir, sucralfate, telmisartan or zolmitriptan. No interaction of any kind has been reported with alpha-1 adrenergic blockers (doxazosin, terazosin), furosemide, letrozole or zanamivir.

Paracetamol slightly reduces urinary excretion of diazepam, although plasma levels remain unchanged.

Paracetamol does not affect the immunogenicity of influenza vaccines, and could reduce the symptoms of their adverse reactions.

- Sedatives (opioid analgesics, barbiturates, benzodiazepines, antipsychotics). Sedative effects could be potentiated.

- Sympathomimetics. It can produce a potentiation of side effects, both of nervous and cardiovascular origin.

- Zidovudine. Paracetamol could increase the elimination of zidovudine, decreasing its effects.

"INTERACTIONS RELATED TO CHLORPHENAMINE"

- Alcohol or medications that cause depression on the central nervous system: the depressant effects of these medications or antihistamines such as chlorphenamine may be enhanced, and may cause symptoms of overdose.

- Monoamine oxidase inhibitors (MAOIs): their simultaneous use is not recommended because they can prolong and intensify the anticholinergic and central nervous system depressant effects of antihistamines.

- Tricyclic antidepressants or maprotiline (tetracyclic antidepressant) or other medications with anticholinergic action: the anticholinergic effects of these medications or antihistamines such as chlorphenamine may be potentiated. If gastrointestinal problems develop, patients should be warned to notify the doctor as soon as possible, as paralytic ileus could occur.

- Ototoxic drugs: symptoms of ototoxicity such as tinnitus, dizziness and vertigo can be masked.

- Photosensitizing drugs: additive photosensitizing effects may be caused.

"INTERACTIONS RELATED TO DEXTROMETHORPHAN"

- Expectorants and mucolytics. Inhibition of the cough reflex could lead to pulmonary obstruction in the event of increased volume or fluidity of bronchial secretions.

- Hypnotics. Risk of potentiation of the sedative effect when associated with alcohol or drugs such as barbiturates, benzodiazepines, H1 antihistamines, other opioid analgesics or antipsychotics.

- Enzyme inhibitors. Dextromethorphan is a CYP2D6 substrate, so its effects and toxicity could be increased when associated with drugs such as abiraterone, antiarrhythmics (amiodarone, flecainide), bupropion, coxibs, imatinib, or terbinafine. Reduce the dose of dextromethorphan if the association is necessary.

Avoid consumption of grapefruit juice or bitter oranges, which can inhibit CYP2D6 and 3A4.

The association of dextromethorphan with certain CYP2D6 inhibitors such as MAOIs, drugs with MAOI activity (eg linezolid, procarbazine) or SSRIs (eg paroxetine) has been associated with the development of severe serotonergic syndrome. The association is contraindicated, and these medications must be distanced for at least 14 days.

Combine with caution other serotonergic drugs such as tricyclic antidepressants.

- Memantine. Dextromethorphan could potentiate the toxicity of memantine. Avoid association.

"INTERACTIONS RELATED TO PSEUDOEPHEDRINE"

- Urinary acidifiers (ammonium chloride). The administration of ammonium chloride or any other acidifying drug could favor the elimination of pseudoephedrine, since this drug is a basic amine. A decrease in pharmacological activity could occur.

- Urinary alkalinizers (sodium bicarbonate). Cases of patients have been described in whom the elimination half-life of pseudoephedrine increased by 71-100% after administration of a urinary alkalinizer. This effect could be due to the lower solubility of pseudoephedrine in basic urine, as it is a weak base.

- Inhalation anesthetics. Administration of pseudoephedrine before or shortly after anesthesia with these anesthetics could increase the risk of serious ventricular arrhythmias, especially in patients with pre-existing heart disease, as anesthetics greatly sensitize the myocardium to the effects of sympathomimetics. In the event that the patient is going to undergo a scheduled surgical intervention, it is recommended to suspend the administration of this medication at least 24 hours before the operation.

- Tricyclic antidepressants. Tricyclic antidepressants could potentiate the vasopressor effects of sympathomimetic amines, leading to hypertensive crises. It is recommended to avoid the association.

- Antihypertensives. Co-administration of pseudoephedrine together with antihypertensives such as beta-blockers, methyldopa or diuretics could reduce antihypertensive activity, due to the vasopressor effects of pseudoephedrine. In addition, beta-blockers have given rise to cases of hypertensive crisis when administered with pseudoephedrine, due to beta-blockade, which favors increased binding of pseudoephedrine to alpha-adrenergic receptors. Periodic monitoring of heart function and blood pressure is recommended.

- Digoxin. Simultaneous administration of digoxin with pseudoephedrine could increase the risk of cardiac arrhythmias.

- Nerve stimulants (amphetamines, cocaine, xanthines). Co-administration could potentiate nerve stimulation, leading to intense excitability. It is recommended to avoid the association. Cocaine might also increase cardiovascular side effects.

- Guanethidine. Pseudoephedrine opposes the sympatholytic effects of guanethidine, both by stimulating norepinephrine release and by binding to alpha-1 receptors. There is a risk of losing the therapeutic effects of guanethidine, resulting in hypertension. It is recommended to avoid the association.

- Thyroid hormones. Potentiation of the effects of both drugs could occur, with the risk of arterial hypertension and coronary insufficiency.

- MAOI (including linezolid). MAOIs have led to potentiation of the effects of pseudoephedrine due to inhibition of norepinephrine metabolism, intensifying and prolonging the vasopressor and cardiac stimulant effects, and giving rise to headache, cardiac arrhythmias, vomiting, or sudden and intense hypertensive and/or hyperpyretic crises. Pseudoephedrine should not be administered during MAOI treatment or for 14 days after treatment with these drugs.

- Levodopa. The administration of levodopa together with sympathomimetics increases the risk of cardiac arrhythmias, so a decrease in the dose of the adrenergic agonist may be necessary.

- Nitrates. Pseudoephedrine acts as a vasoconstrictor, so it could antagonize the antianginal effects of nitrates. It is recommended to avoid the association.

- Reserpine. Reserpine administration may result in reduced effects of indirect sympathomimetics such as pseudoephedrine, probably due to depletion of noradrenergic vesicles by reserpine. It is recommended to avoid the association.

- Sympathomimetics. Potentiation of the cardiovascular and neurological effects of both drugs could occur. It is recommended to avoid the association.

PREGNANCY

Animal safety:

* Paracetamol: reproduction studies do not show malformations or phototoxic effects. Therefore, under normal conditions of use, paracetamol can be used during pregnancy, after benefit-risk assessment.

* Chlorphenamine maleate: Animal studies have not shown adverse effects on the fetus.

* Dextromethorphan: Long-term, high doses of dextromethorphan produced histologic changes in the liver, kidneys, and lungs, decreased growth curve, and transient anemia in rats treated with dextromethorphan orally.

* Pseudoephedrine: pseudoephedrine is not very toxic when administered orally; while it presents greater toxicity when administered parenterally. The lowest lethal dose of pseudoephedrine reported in animals is approximately 104 times higher than the exposures that occurred from its use at recommended doses.

Safety in humans:

* Paracetamol: they do not produce undesirable effects in the pregnant woman, in the fetus, or in the newborn.

* Chlorphenamine maleate: There are no adequate and well-controlled studies in humans.

* Dextromethorphan: There are no adequate and well-controlled studies in humans. However, the use of this drug can be accepted in the absence of safer therapeutic alternatives, and provided that the benefits outweigh the possible risks.

* Pseudoephedrine: the use of pseudoephedrine during the first trimester has been associated with slight increases in the risk of the appearance of 3 types of malformations: gastroschisis and small bowel atresia due to vascular disruption, and hemifacial microsomia.

Therefore, it is contraindicated in the first trimester of pregnancy.

In conclusion, there are insufficient data on the use of the combination of these active principles of this drug in pregnant women to ensure its safety in this population.

This medicine should not be used during pregnancy unless there are no safer therapeutic alternatives, and provided that the benefits outweigh the possible risks.

Effects on fertility:

* Paracetamol: chronic toxicity studies in animals show that high doses of paracetamol cause testicular atrophy and inhibition of spermatogenesis; the significance of this fact for its use in humans is unknown.

* Chlorphenamine maleate: no data available.

* Dextromethorphan: no relevant mutagenicity, teratogenicity or fertility problems have been reported in animals treated with dextromethorphan

* Pseudoephedrine: reduces the average weight, length and ossification index of the fetal skeleton. An association between the use of pseudoephedrine and the development of cancer has not been observed.

LACTATION

- Paracetamol: can be used in lactating women if the recommended dose is not exceeded. Caution should be exercised in the case of prolonged use.

- Chlorphenamine maleate: can inhibit lactation due to its anticholinergic actions. Small amounts of antihistamines are excreted in breast milk, their use is not recommended during lactation.

- Dextromethorphan: there are no data on the excretion of dextromethorphan in breast milk, although no problems have been demonstrated in humans.

- Pseudoephedrine: excreted in breast milk in small amounts. Its use in lactating women is not recommended because sympathomimetic amines pose a greater risk of side effects for the infant, especially newborns and premature infants.

The administration of this medication is not recommended during the lactation period.

CHILDREN

The safety and efficacy of this medication in children <12 years of age have not been evaluated, therefore its use is not recommended.

ADVANCED AGE

Elderly patients may be more susceptible to the adverse effects of this medication, so it is recommended to use it with caution, and to discontinue its administration if the adverse reactions are not tolerable.

EFFECTS ON DRIVING

This medicine can substantially affect the ability to drive and/or operate machinery. Patients should avoid operating dangerous machinery, including automobiles, until they are reasonably certain that drug treatment will not adversely affect them.

ADVERSE REACTIONS

Adverse reactions are described according to each frequency interval, being considered very common (>10%), common (1-10%), uncommon (0.1-1%), rare (0.01-0.1%), very rare (<0.01%) or unknown frequency (cannot be estimated from the available data).

"RAMS RELATED TO PARACETAMOL"

- Liver disorders: rare [INCREASED TRANSAMINASES], [INCREASED ALKALINE PHOSPHATASE], [HIPERBILIRRUBINEMIA]; very rare [HEPATOTOXICITY], with [JAUNDICE].

- Cardiovascular disorders: rare [HYPOTENSION].

- Nervous system disorders: [DIZZENESS], [DISORIENTATION], [EXCITABILITY].

- Genitourinary disorders: very rare renal disorders such as cloudy urine and kidney disorders.

- Immune system disorders: very rare [HYPERSENSITIVITY REACTIONS], with symptoms from [SKIN ERUPTIONS] and [URTICARIA] to [ANAPHYLAXIS].

- Hematological disorders: very rare [THROMBOCYTOPENIA], [AGRANULOCYTOSIS], [LEUKOPENIA], [NEUTROPENIA], [HEMOLYTIC ANEMIA], [METAHEMOGLOBINEMIA]. The prothrombin time could be increased, although it does not seem significant.

- Metabolic disorders: very rare [HYPOGLYCEMIA].

- Analytical: analytical alterations have been described such as [INCREASE IN LACTATE DEHYDROGENASE], [INCREASE IN SERUM CREATININE], increase in ammonia levels, [INCREASE IN UREIC NITROGEN].

On the other hand, paracetamol could interfere with the analytical determination of uric acid and glucose, as well as with theophylline monitoring. It can also give false positives in the determination of 5-hydroxy-indoleacetic acid when nitrosonaphthol is used as a reagent.

- General: rare [GENERAL DISCOMFORT].

"RAMS RELATED TO CHLORPHENAMINE"

- Nervous system disorders: very common [SLEEPY]; frequent [DIZZINES].

- Gastrointestinal disorders: frequent [DYSPEPSIA], [PHARYNGITIS], [DRY MOUTH].

- General disorders and administration site conditions: [AGITATION]

"RAMS RELATED TO DEXTROMETHORPHAN"

- Immune system disorders: unknown frequency [HYPERSENSITIVITY REACTIONS] including [ANAPHYLAXIA], [ANGIOEDEMA], [URTICARIA], [PRURITUS], rash and [ERYTHEMA].

- Psychiatric disorders: very rare [HALLUCINATIONS], [OPIOID DEPENDENCE].

- Nervous system disorders: common [DIZZINES]; very rare [SLEEP]; unknown frequency [HEADACHE], [CONFUSION].

- Gastrointestinal disorders: frequent [NAUSEA], [VOMITING], and intestinal discomfort; frequency unknown [CONSTIPATION].

- Skin and subcutaneous tissue disorders: frequency unknown [DRUG ERUPTION].

- General disorders and alterations at the administration site: frequent [FATIGUE].

"RAMS RELATED TO PSEUDOEPHEDRINE"

- Digestive disorders. [NAUSEA], [VOMITING], [DYSPEPSIA] and [DRY MOUTH] may appear.

- Nervous system disorders: frequent [NERVOUSNESS], [EXCITABILITY], [INSOMNIA], [DIZZNESS] or [VERTIGO]. More rarely, cases of [ASTENIA], [CEFALEA] and [TREMBOR] have been described. In more serious cases, and normally associated with overdose, [ANXIETY], [SLEEP], [CONVULSIONS] and [HALLUCINATIONS] could appear.

- Cardiovascular disorders: Pseudoephedrine can lead to [CARDIAC ARRYTHMIA], with [TACHYCARDIA] and [PALPITATIONS], especially at high doses or in patients predisposed to sympathomimetic effects. It can also produce [ARTERIAL HYPERTENSION] and [BRADICARDIA] reflected.

- Respiratory disorders: [DYSPNEA].

- Genitourinary disorders: [URINARY RETENTION] may occasionally appear in patients with prostatic hypertrophy.

- Ophthalmological disorders. Cases of [BLEPHAROSPASM], with [PHOTOFOBIA] and [TEARING] have been described.

- Skin and subcutaneous tissue disorders: Cases of [HYPERSENSITIVITY REACTIONS], with [URTICARIA] and [CUTANEOUS ERUPTIONS] have been described. In the most serious cases [LEUKOPENIA], [AGRANULOCYTOSIS] and [TROMBOCYTOPENIA] have appeared.

- General disorders and alterations at the administration site: [HYPERHIDROSIS], [PALITY].

OVERDOSE

*Paracetamol

Symptoms: Overdose from paracetamol products is a very serious and potentially fatal poisoning. The symptoms may not manifest immediately, and may even take up to three days to appear. These symptoms include confusion, excitability, restlessness, nervousness and irritability, dizziness, nausea and vomiting, loss of appetite and liver damage. Hepatotoxicity usually manifests within 48-72 hours with nausea, vomiting, anorexia, malaise, diaphoresis, jaundice, abdominal pain, diarrhea, and liver failure.

In children it also appears states of drowsiness and alterations in the way of walking.

In the most severe cases, the patient may die from hepatic necrosis or acute renal failure.

The minimal toxic dose of paracetamol is 6 g in adults and 100 mg/kg in children. Doses greater than 20-25 g of paracetamol are potentially fatal.

Treatment: In case of overdose, you should go immediately to a medical center, since paracetamol poisoning can be fatal, even if there are no symptoms. Early identification of paracetamol overdose is especially important in children, due to the severity of the condition, as well as the existence of a possible treatment.

In any case, proceed initially with gastric lavage and aspiration of the stomach contents, preferably within four hours of ingestion. The administration of activated carbon can reduce the amount absorbed.

There is a specific antidote in case of paracetamol poisoning, N-acetylcysteine. It is recommended to administer a dose of 300 mg/kg of N-acetylcysteine, equivalent to 1.5 ml/kg of a 20% aqueous solution, with a pH of 6.5, intravenously, over a period of 20 hours and 15 minutes, according to the following scheme:

- Adults. Initially, a shock dose of 150 mg/kg (0.75 ml/kg of 20% solution) will be administered by slow intravenous route over 15 minutes, either directly or diluted in 200 ml of 5% dextrose.

A maintenance dose will then be instituted with 50 mg/kg (0.25 ml/kg of 20% solution) in 500 ml of 5% dextrose by slow intravenous infusion over 4 hours.

Finally, 100 mg/kg (0.50 ml/kg of 20% solution) will be administered in 1000 ml of 5% dextrose as a slow intravenous infusion over 20 hours.

- Children. The same amounts will be administered per unit weight as in adults, but the volumes of dextrose must be adjusted based on the age and weight of the child in order to avoid vascular congestion.

The effectiveness of the antidote is maximum if it is administered within 8 hours of ingestion. The effectiveness decreases progressively thereafter and is ineffective after 15 hours.

The administration of 20% N-acetylcysteine ​​may be discontinued when blood paracetamol levels are less than 200 µg/ml.

In addition to the administration of the antidote, a symptomatic treatment will be established, keeping the patient under clinical surveillance.

In the event of hepatotoxicity, it is advisable to perform a liver function study and repeat the study at 24-hour intervals.

* Chlorphenamine:

Symptoms of chlorphenamine overdose (deep sedation, anticholinergic symptoms) may appear.

* Dextromethorphan:

Dextromethorphan overdose does not usually cause severe symptoms, although increased sedation is to be expected.

* pseudoephedrine

Pseudoephedrine overdose produces symptoms related to cardiovascular and central nervous system stimulation. Like other sympathomimetic agents, symptoms of overdose include: rapid breathing, excitement, nervousness, irritability, restlessness, tremors, convulsions, palpitations, hypertension, arrhythmias, urination difficulty, insomnia, mydriasis, anxiety, agitation, hallucinations, tachycardia, and reflex bradycardia. In severe cases, hypokalemia, psychosis, seizures, coma, hypertensive crisis, dysrhythmias, cerebral hemorrhage, myocardial infarction, rhabdomyolysis, and ischemic intestinal infarction may appear. Emetics and gastric lavage must be started within 4 hours of overdose to be effective. Absorbent charcoal is only useful if administered within the first hour. In pseudoephedrine poisoning, forced diuresis will increase its elimination, as long as renal function is adequate. However, in cases of severe overdose, diuresis is not recommended. Monitor cardiac function and quantify serum electrolytes. If there are signs of cardiac toxicity, the use of IV propranolol may be indicated. Hypokalemia can be treated with a slow infusion of a dilute potassium chloride solution, monitoring the serum potassium concentration during administration and for several hours afterwards. In case of delirium and convulsions, administer IV diazepam, pseudoephedrine In pseudoephedrine poisoning, forced diuresis will increase its elimination, as long as renal function is adequate. However, in cases of severe overdose, diuresis is not recommended. Monitor cardiac function and quantify serum electrolytes. If there are signs of cardiac toxicity, the use of IV propranolol may be indicated. Hypokalemia can be treated with a slow infusion of a dilute potassium chloride solution, monitoring the serum potassium concentration during administration and for several hours afterwards. In case of delirium and convulsions, administer IV diazepam, pseudoephedrine In pseudoephedrine poisoning, forced diuresis will increase its elimination, as long as renal function is adequate. However, in cases of severe overdose, diuresis is not recommended. Monitor cardiac function and quantify serum electrolytes. If there are signs of cardiac toxicity, the use of IV propranolol may be indicated. Hypokalemia can be treated with a slow infusion of a dilute potassium chloride solution, monitoring the serum potassium concentration during administration and for several hours afterwards. In case of delirium and convulsions, administer IV diazepam, pseudoephedrine Monitor cardiac function and quantify serum electrolytes. If there are signs of cardiac toxicity, the use of IV propranolol may be indicated. Hypokalemia can be treated with a slow infusion of a dilute potassium chloride solution, monitoring the serum potassium concentration during administration and for several hours afterwards. In case of delirium and convulsions, administer IV diazepam, pseudoephedrine Monitor cardiac function and quantify serum electrolytes. If there are signs of cardiac toxicity, the use of IV propranolol may be indicated. Hypokalemia can be treated with a slow infusion of a dilute potassium chloride solution, monitoring the serum potassium concentration during administration and for several hours afterwards. In case of delirium and convulsions, administer IV diazepam, pseudoephedrine

DOPING

Pseudoephedrine is a prohibited substance during competition.

It is prohibited when its administration gives rise to a concentration in urine greater than 150 mcg/ml.

Detection in a sample during competition of any amount of pseudoephedrine in combination with a diuretic or masking agent will be considered an Adverse Analytical Finding unless the athlete has obtained an Approved Therapeutic Use Exemption (TUE) for ephedrine in addition to that granted for the diuretic or masking agent.

It is considered a "specific substance" and, therefore, a violation of the rule in which this substance is involved may cause a reduction in sanction as long as the athlete can demonstrate that the use of the specific substance in question was not with the intention of increasing his sporting performance.

Leaflet Grippal With Pseudoephedrine And Dextromethorphan 16 Capsules