Grippal With Phenylephrine 10 Envelopes Granules For Oral Solution

Grippal With Phenylephrine 10 Envelopes Granules For Oral Solution

Paracetamol / Phenylephrine bitartrate / Chlorphenamine maleate

ACTION AND MECHANISM

- Flu.

* Paracetamol: analgesic and antipyretic, probably due to the inhibition of cyclooxygenase at the central level, especially COX-2, decreasing the synthesis of prostaglandins.

* Chlorphenamine: H1 antihistamine and anticholinergic. Reduces cold symptoms such as sneezing, tearing or runny nose.

* Phenylephrine: alpha-1 adrenergic agonist. Produces vasoconstriction, reducing nasal congestion.

INDICATIONS

- Symptomatic treatment of [COMMON COLD] or [FLU] that present with mild or moderate pain, fever, congestion and runny nose in adults and adolescents from 15 years of age.

POSOLOGY

- Adults and adolescents > 15 years: 1 envelope/6-8 h. Maximum dose 4 sachets/24 h.

- Children < 15 years: not recommended because the paracetamol content is not adjusted for this age.

- Elderly: no specific dosage recommendations have been made. Use with caution.

Duration of treatment: consult the doctor and/or pharmacist if the symptoms continue for more than 3 days (fever) or 5 days (pain and other symptoms), or if new symptoms appear. Discontinue treatment when symptoms disappear.

Forgotten dose: administer the missed dose as soon as possible, unless there is a short time left for the next one. Administer the next dose at the usual time. Do not double the next dose.

DOSAGE IN RENAL FAILURE

It is not recommended since the paracetamol content exceeds the recommended dose in these patients.

DOSAGE IN LIVER FAILURE

- Mild to moderate hepatic impairment (Child-Pugh classes A and B): maximum dose 3 sachets/24 h, with a minimum interval between doses of 8 h.

- Severe hepatic impairment (Child-Pugh class C): contraindicated.

RULES FOR CORRECT ADMINISTRATION

- Envelopes: dissolve the contents of the envelope in half a glass of liquid, preferably water.

Administration with food: can be taken with or without food.

CONTRAINDICATIONS

- Hypersensitivity to any component of the medication, including [ALLERGY TO PARACETAMOL]. Cross hypersensitivity reactions may exist between different antihistamines.

- Pathologies that could be aggravated by this medication, such as [ARTERIAL HYPERTENSION], [PHEOCHROMOCYTOMA], [HYPERTHYROIDISM], [ISCHEMIC HEART DISEASE], [TACHYCARDIA], [GLAUCOMA] or [DIABETES].

- Severe renal insufficiency (CrCl < 30 ml/min) or severe hepatic insufficiency (Child-Pugh class C).

- [PORFYRIA]. H1 antihistamines have been associated with the appearance of porphyric outbreaks, so they are not considered safe in these patients.

- Patients being treated with an MAOI in the previous 14 days (see Interactions; antidepressants).

- Treatment with beta-blockers or other sympathomimetics.

PRECAUTIONS

- [RENAL INSUFFICIENCY]. In general, the use in patients with renal failure is not recommended, since a dosage readjustment is required that would not be possible with this drug (see Dosage in renal failure for more information).

- [HEPATOTOXICITY]. Paracetamol has been associated with hepatotoxicity phenomena when used at high doses (> 4 g/24 h) or for prolonged periods of time.

Assess its use in case of [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 levels of glutathione, or treated with other hepatotoxic drugs.

Paracetamol doses should not generally exceed 3 g/24 h.

Avoid the administration of other medications that contain paracetamol, as well as the consumption of alcoholic beverages during treatment.

- [ALLERGY TO SALICYLATES]. Patients allergic to acetylsalicylic acid do not usually present cross hypersensitivity reactions with paracetamol, but cases of mild bronchospasm have been reported, so caution is advised in case of [ASTHMA].

- Patients with pathologies that could be aggravated by anticholinergic or sympathomimetic effects, such as [CONSTIPATION], [INTESTINAL OBSTRUCTION], [HIATUS HERNIA], [GASTROESOPHAGIC REFLUX DISEASE], [PEPTIC ULCERA] stenosing, [ULCEROUS COLITIS], [HEART FAILURE], [ATHEROSCLEROSIS], [PERIPHERAL ARTERIOPATHY], [ANEURYSM], [PROSTATIC HYPERPLASIA] or other causes of [URINARY RETENTION].

- Skin tests for hypersensitivity to allergenic extracts. Due to their antihistamine effects, they could give false negatives in diagnostic tests using these extracts. It is recommended to suspend the administration at least 72 hours before performing the test.

- Situations that could raise body temperature. Anticholinergic drugs could interfere with the body's thermoregulatory capacity, so they could favor the appearance of heat strokes in patients exposed to extreme heat, especially the elderly, who perform intense physical exercise with inappropriate clothing or hours, or in treatment with drugs such as diuretics or others that favor [DEHYDRATION].

ADVICE TO THE PATIENT

- Avoid drinking alcohol during treatment.

- Do not exceed recommended doses. The administration of other drugs with paracetamol could lead to very serious poisoning.

- Consult your doctor and/or pharmacist if the pain continues after 5 days of treatment, the fever lasts for more than 3 days, or the symptoms worsen or new ones appear.

- Avoid driving or carrying out activities that require your attention until you verify that the treatment does not affect you negatively.

- Tell your doctor and/or pharmacist if you are going to undergo allergy diagnostic tests.

- Tell your doctor and/or pharmacist if you have any of these symptoms:

* Dry mouth, visual disturbances, constipation or inability to urinate.

SPECIAL WARNINGS

- In case the patient experiences difficulty urinating or urine retention, it is recommended to stop the treatment.

- Patients who are going to undergo allergy tests with the use of allergenic extracts should stop treatment at least 72 hours before, to avoid false negatives.

INTERACTIONS

- Ethyl alcohol. Ethyl alcohol could potentiate the sedative effects of this medicine. Also, drinking alcoholic beverages together with paracetamol could cause liver damage. It is recommended to avoid alcohol intake during treatment. In chronic alcoholics, no more than 2 g/24 hours of paracetamol should be administered.

- Alpha blockers (antimigraine ergotamines, oxytocin). Its simultaneous use is not recommended because it may cause an increase in vasoconstrictor effects. Alpha blockers for antihypertensives or for benign prostatic hyperplasia, by not blocking beta receptors, can cause an increased risk of hypotension and tachycardia.

- Inhaled anesthetics (halothane). They can increase the risk of arrhythmias.

- Oral anticoagulants. On very rare occasions, usually with high doses, the anticoagulant effects could be potentiated by inhibition of the hepatic synthesis of coagulation factors by paracetamol. It is recommended to administer the minimum dose, with the lowest possible duration of treatment, and to control the INR.

- Anticholinergics (antiparkinsonians, tricyclic antidepressants, MAOIs, neuroleptics). Chlorphenamine could potentiate the anticholinergic effects, so it is recommended to avoid the association.

- Oral contraceptives. They could increase the plasmatic clearance of paracetamol, decreasing its effects.

- Tricyclic antidepressants (amitriptyline, amoxapine, clomipramine, desipramine, doxepin, maprotiline). Its simultaneous use can potentiate the pressor effects of phenylephrine.

- Antihypertensives (beta blockers, diuretics, guanethidine, methyldopa). Phenylephrine could antagonize the antihypertensive effects, and even lead to hypertensive crises, so it is recommended to monitor blood pressure. Propranolol could inhibit the metabolism of paracetamol, leading to toxic effects.

- Atropine. It blocks reflex bradycardia caused by phenylephrine and increases the pressor response to phenylephrine.

- Activated carbon. It can produce an adsorption of paracetamol, decreasing its absorption and pharmacological effects.

- Chloramphenicol. The toxicity of chloramphenicol could be potentiated, probably by inhibition of its metabolism.

- Digital. The risk of cardiac arrhythmias associated with phenylephrine may be increased.

- Diuretics that can cause hypokalemia (furosemide). Hypokalemia may be potentiated and arterial sensitivity to vasopressors such as phenylephrine may be decreased.

- Nerve stimulants (amphetamines, cocaine, xanthines). Nerve stimulation could be enhanced, leading to intense excitability.

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

- MAOI. MAOIs could potentiate the effects of phenylephrine by inhibiting the metabolism of norepinephrine, increasing the risk of hypertensive crises and other cardiac phenomena. It is recommended to avoid the administration of this drug in patients treated with MAOIs in the previous 14 days.

- Enzyme inducers. Medications such as barbiturates, carbamazepine, hydantoin, isoniazid, rifampicin, or sulfinpyrazone could induce the metabolism of paracetamol, decreasing its effects and increasing the risk of hepatotoxicity.

- Lamotrigine. Paracetamol could reduce the serum concentrations of lamotrigine, leading to a decreased therapeutic effect.

- 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.

- Metoclopramide and domperidone. They increase the absorption of paracetamol in the small intestine, due to the effect of these drugs on gastric emptying.

- Probenecid. Increases the plasmatic half-life of paracetamol, by decreasing the degradation and urinary excretion of its metabolites.

- Ion exchange resins (cholestyramine). Decreased absorption of paracetamol, with possible inhibition of its effect, due to fixation of paracetamol in the intestine.

- Nitrates. Phenylephrine could antagonize the antianginal effects of nitrates, so it is recommended to avoid the association.

- 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. Although a possible potentiation of zidovudine toxicity (neutropenia, hepatotoxicity) has been described in isolated patients, there does not appear to be any kinetic interaction between the two drugs.

PREGNANCY

Animal safety : Phenylephrine was associated with increased fetal mortality and preterm labor in rabbits, as well as decreased uterine blood flow in sheep.

Studies with paracetamol in animals have not shown cases of malformations or fetotoxic effects.

Safety in humans : Adequate and well-controlled studies in humans are not available. Its administration is only accepted if there are no safer therapeutic alternatives, and the benefits outweigh the possible risks.

Effects on fertility : No specific studies in humans have been performed.

LACTATION

Excretion in milk:

- Paracetamol: small amounts (similar to maternal cp).

- Chlorphenamine: unknown. Other antihistamines do.

- Phenylephrine: limited excretion and reduced oral bioavailability.

The consequences that it could have for the infant are unknown. It is recommended to avoid its administration during lactation.

CHILDREN

It can be used in adolescents from 15 years at the same doses as in adults.

Its use is not recommended in children and adolescents <15 years of age because paracetamol doses are not adjusted for this age.

ADVANCED AGE

No specific problems have been described in the elderly that require a dose readjustment.

However, these patients could be more sensitive to the side effects of this drug, so it is advisable to use it with caution, especially watching for the appearance of anticholinergic effects.

EFFECTS ON DRIVING

It can produce significant sedation due to the presence of chlorphenamine. 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).

"PARACETAMOL RAM"

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

- Cardiovascular: rare [HYPOTENSION].

- Neurological/psychological: [DIZZENESS], [DISORIENTATION], [EXCITABILITY].

- Genitourinary: very rare renal disorders such as cloudy urine and kidney disorders; unknown frequency [INCREASED SERUM CREATININE], increased ammonia levels, [INCREASED UREA NITROGEN].

- Allergic: very rare [HYPERSENSITIVITY REACTIONS], with symptoms ranging from [SKIN ERUPTIONS] and [URTICARIA] to [ANAPHYLAXIS].

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

- Metabolic: very rare [HYPOGLYCEMIA]; frequency unknown [INCREASED LACTATE DEHYDROGENASE].

- General: rare [GENERAL DISCOMFORT].

"CHLORPHENAMINE RAM"

- Digestive: unknown frequency [NAUSEA], [VOMITING], [DIARRHEA], [CONSTIPATION], [ABDOMINAL PAIN], [DRY MOUTH].

- Hepatic: unknown frequency [HEPATITIS], [CHOLESTASIS].

- Cardiovascular: unknown frequency [PALPITATIONS], [HYPOTENSION], [ARTERIAL HYPERTENSION].

- Neurological/psychological: unknown frequency [SOMNOLENCE], [DIZZNESS], facial [DYSTONIA], [ATAXIA], [TREMBOR], [PARESTHESIS], [DYSGEUSIA], [PAROSMIA].

Paradoxical excitability reactions may appear in children and the elderly, with [AGITATION], [INSOMNIA], [NERVOUSNESS], [DELIRIO], [CONVULSIONS].

- Respiratory: unknown frequency [NASAL DRYNESS] or throat, [SORE THROAT], thickening of mucus, [CHEST TIGHTNESS], [WHEELING].

- Genitourinary: unknown frequency [URINARY RETENTION] or difficulties urinating, [SEXUAL IMPOTENCE], early menstruation.

- Dermatological: unknown frequency [HYPERHIDROSIS].

- Allergic: unknown frequency [HYPERSENSITIVITY REACTIONS], with symptoms such as [TOS], [DYSPHAGIA], [TACHYCARDIA], [URTICARIA], facial [EDEMA] or [ANGIOEDEMA], [DYSPNEA], [FATIGUE]. Also [PHOTOSENSITIVITY REACTIONS].

- Osteomuscular: unknown frequency [MIASTENIA].

- Ophthalmological: unknown frequency [BLURRED VISION], [DIPLOPIA].

- Otic: unknown frequency [TINNITUS], [LABERINTITIS].

- Hematological: unknown frequency [AGRANULOCYTOSIS], [LEUKOPENIA], [APLASTIC ANEMIA], [TROMBOCYTOPENIA], [HEMORRHAGE].

- Metabolic: unknown frequency [ANOREXIA].

- General: unknown frequency [FATIGUE], [EDEMA].

"RAM OF PHENYLEPHRINE"

- Digestive: unknown frequency [VOMITING], [HIPERSALIVATION].

- Cardiovascular: unknown frequency [ARTERIAL HYPERTENSION], [HYPOTENSION], [BLUENESS], [BRADICARDIA], [TACHYCARDIA], [ANGINA PECTOR], [PALPITATIONS], [CARDIAC ARREST].

- Neurological/psychological: unknown frequency [HEADACHE], [CEREBRAL HEMORRHAGE], [VERTIGO], [DIZZENESS], dullness.

- Respiratory: unknown frequency [DYSPNEA], [PULMONARY EDEMA].

- Genitourinary: unknown frequency [VACILANT MICTION], [URINARY RETENTION].

- Dermatological: unknown frequency [HYPERHIDROSIS], [PARESTHEIA].

- Metabolic: unknown frequency [HYPERGLYCEMIA], [HYPOGLYCEMIA].

- General: unknown frequency sensation of cold on the skin.

ADVERSE REACTIONS RELATING TO EXCIPIENTS

- This medicine contains mannitol. Daily doses greater than 10 g can produce a certain mild laxative effect and lead to [DIARRHEA].

OVERDOSE

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.

In addition to the symptoms of paracetamol overdose, symptoms of chlorphenamine overdose (deep sedation, anticholinergic symptoms) and phenylephrine (excitability, convulsions, tachycardia, arterial hypertension) may appear.

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 mcg/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.

Leaflet Grippal With Phenylephrine 10 Envelopes Granules For Oral Solution