ACTION AND MECHANISM

- Flu medication.

* Ibuprofen: A nonsteroidal anti-inflammatory drug (NSAID) with analgesic and antipyretic properties. It works by inhibiting prostaglandin synthesis through the competitive and reversible inhibition of various cyclooxygenase (COX) isoforms, both peripherally and in the central nervous system. The analgesic and anti-inflammatory effects are related to the inhibition of prostaglandin (PG) synthesis. The antipyretic action is related to the inhibition of PGE2 synthesis.

* Chlorphenamine: an H1 antihistamine and anticholinergic. It reduces cold symptoms such as sneezing, watery eyes, and runny nose.

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

CONTRAINDICATIONS

- Hypersensitivity to ibuprofen, chlorphenamine or phenylephrine or to any other component of the medication.

Due to a possible cross-reactivity between ibuprofen and acetylsalicylic acid or other NSAIDs, this medicine should not be administered in cases of salicylate allergy or NSAID allergy. These allergic reactions are especially common in patients with asthma, nasal polyps, or who have experienced rhinitis, angioedema, or urticaria when receiving another NSAID or salicylates.

- Active or recurrent peptic ulcer, active inflammatory bowel disease, or any other condition that increases the risk of gastrointestinal bleeding. Ibuprofen has ulcerogenic effects due to the inhibition of prostaglandin synthesis, which could increase the risk of gastrointestinal bleeding and perforation.

- Severe renal impairment (CLcr < 30 ml/min). Safety and efficacy have not been evaluated, therefore its use is not advised.

- Severe hepatic impairment (Child-Pugh class C). Safety and efficacy have not been evaluated, therefore use is not advised.

- Severe heart failure (NYHA class III-IV) or uncontrolled hypertension. Fluid retention could worsen these conditions.

- Serious cardiovascular diseases (such as coronary artery disease, angina).

- Tachycardia.

- [COAGULATION DISORDERS]. Ibuprofen has antiplatelet effects, although less potent and longer-lasting than those of acetylsalicylic acid. Therefore, it may increase bleeding time, so it should be used with caution in patients with [HEMORRHAGIC DIATHESIS] or active [HEMORRHAGE].

- [HYPERTHYROIDISM], [HIGH BLOOD PRESSURE]. Due to its phenylephrine content, there is a risk of hypertensive crisis.

- Diabetes mellitus.

- Patients treated with an MAOI in the previous 2 weeks (see Interactions, phenylephrine).

- Patients undergoing treatment with sympathomimetic drugs, with beta-blockers (see Interactions).

- Concomitant use with NSAIDs including specific cyclooxygenase-2 inhibitors (see Interactions).

- [GLAUCOMA]. The anticholinergic mydriatic effect of chlorphenamine may increase intraocular pressure.

- Pregnancy. The use of ibuprofen is contraindicated during the third trimester of pregnancy, and its use is not recommended for prolonged periods of time during the first two trimesters.

- Adolescents and children under 12 years old.

ADVANCED AGE

Elderly patients may require lower doses. Caution is advised as they are more susceptible to NSAID-related adverse effects, primarily gastrointestinal bleeding and perforation.

PREGNANCY

- Animal safety: no data available.

- Safety in humans: * Ibuprofen: Inhibition of prostaglandin synthesis adversely affects pregnancy and/or embryo-fetal development. Epidemiological studies suggest an increased risk of miscarriage and cardiac malformation and gastroschisis after the use of prostaglandin synthesis inhibitors in early pregnancy. The absolute risk of cardiovascular malformations increased by less than 1%, to approximately 1.5%. The risk is presumed to increase with the dose and duration of therapy. From the 20th week of pregnancy onward, ibuprofen use may cause oligohydramnios as a result of fetal renal dysfunction. This may occur shortly after the start of treatment and is usually reversible upon discontinuation. In addition, there have been reports of constriction of the ductus arteriosus following treatment in the second trimester, most of which resolved after discontinuation of treatment. Therefore, ibuprofen should not be administered during the first and second trimesters of pregnancy unless absolutely necessary. If ibuprofen is used in women who wish to become pregnant or during the first or second trimester of pregnancy, the dose should be as low as possible and the treatment as short as possible. Prenatal screening for oligohydramnios and constriction of the ductus arteriosus should be considered after exposure to Couldina with ibuprofen for several days from the 20th week of gestation onward. Treatment with Couldina with ibuprofen should be discontinued if oligohydramnios or constriction of the ductus arteriosus is found.

* Phenylephrine: No controlled studies have been conducted in humans. It causes contraction of smooth muscles, including the urinary sphincter and the uterus. Sympathomimetics with vasoconstrictor effects may reduce placental perfusion and should therefore not be used during pregnancy.

* Chlorphenamine: Animal studies have not shown adverse effects on the fetus, but have shown a decrease in postnatal survival. No controlled studies have been conducted in humans. There is insufficient data on the use of the active ingredients of this medicine in pregnant women.

- Fertility: no data available

INDICATIONS

- Relief of symptoms of [COMMON COLD] and [FLU] accompanied by fever, mild to moderate pain, nasal congestion and runny nose, for adults and children 12 years and over.

INTERACTIONS

"IBUPROFEN-RELATED INTERACTIONS"

- NSAIDs, including low-dose aspirin: the simultaneous use of more than one NSAID should be avoided due to the risk of adverse effects without any increase in therapeutic efficacy. Furthermore, ibuprofen may reduce the antiplatelet efficacy of aspirin when administered together. If both drugs are required, it is advisable to separate the doses (administer ibuprofen 8 hours before or 30 minutes after aspirin).

- Alcohol: toxicity may be increased.

- Aliskiren: possible reduction of the antihypertensive effect of aliskiren (NSAIDs act on the renin-angiotensin system). In patients with impaired renal function (dehydrated or elderly), deterioration of renal function may be precipitated (possible acute renal failure, usually reversible). Caution, especially in the elderly, monitoring the antihypertensive effect and renal function.

- Food: food delays Tmax (from ± 2 h in fasting to ± 3 h after eating), although this has no effect on the amount absorbed.

- Quinolone antibacterials: there are isolated reports of seizures that may have been due to the concomitant use of quinolones and some non-steroidal anti-inflammatory drugs.

- Oral anticoagulants, heparin: possible increase in the anticoagulant effect, with a risk of bleeding. Periodic monitoring of coagulation indices is advised.

- Sulfonylurea antidiabetic drugs (chlorpropamide, glibenclamide, tolbutamide): possible increase in hypoglycemic effects, by reducing renal excretion.

- SSRI antidepressants (fluoxetine, paroxetine, sertraline, citalopram): possible increased risk of bleeding in general, and gastrointestinal bleeding in particular, especially in the elderly and patients with a history of digestive bleeding.

- Antihypertensives (ACE inhibitors, Beta-blockers): possible reduction of the antihypertensive effect.

- Oral bisphosphonates (alendronic acid): possible increased risk of esophagitis and gastric ulcer. Cases have been described with naproxen and alendronate.

- Cyclosporine: the effect of NSAIDs on renal prostaglandins may increase the nephrotoxicity of cyclosporine.

- Antiplatelet agents, including pentoxifylline: there is an increased risk of bleeding in general, and gastrointestinal bleeding in particular. Administer with caution.

- Corticosteroids: possible increase in the incidence of gastric discomfort. However, simultaneous use with glucocorticoids in the treatment of osteoarthritis may provide an additional therapeutic benefit and allows for a reduction in the glucocorticoid dosage.

- Digitalis (digoxin): possible increase in plasma concentrations of the digitalis (in neonates). There is also a risk of worsening heart failure and reduced renal function.

- Diuretics (thiazides, high-ceiling diuretics): risk of reduced natriuretic and diuretic effect. May reduce the antihypertensive action of thiazide diuretics.

- Potassium-sparing diuretics and aldosterone antagonists: possible increased risk of hyperkalemia. Frequent monitoring of serum potassium levels is advised.

- Glitazones (pioglitazone, rosiglitazone): theoretical risk of potentiating edema, which both glitazones and NSAIDs can cause. Caution is advised, and patients should monitor for possible signs of fluid retention and heart failure (swollen ankles, dyspnea).

- Hydralazine: possible decrease in the hypotensive effect.

- Iloprost: possible increased risk of bleeding.

- Lithium, salts: possible increase in lithium toxicity due to a reduction in its elimination.

- Methotrexate (administered at doses of 15 mg/week or higher): possible increase in plasma methotrexate levels, with a risk of toxicity, sometimes very severe. The severity depends largely on the dose of methotrexate used. The risk of interaction is reduced with low doses of methotrexate, such as those used in psoriasis and rheumatoid arthritis.

- Mifepristone: Non-steroidal anti-inflammatory drugs should not be administered within 8-12 days after the administration of mifepristone as they may reduce its effects.

- Paracetamol: simultaneous and prolonged use of paracetamol and NSAIDs may cause an increased risk of adverse kidney effects.

- Pentoxifylline: In patients receiving ibuprofen treatment in combination with pentoxifylline, the risk of bleeding may increase, so monitoring of bleeding time is recommended.

- Potassium supplements: possible increase in potassium levels, with risk of hyperkalemia.

- Ticlopidine: possible increased risk of bleeding.

- Zidovudine: Possible alteration of reticulocytes, with severe anemia appearing one week after the start of NSAID administration. Blood values ​​should be monitored, especially at the start of treatment.

GUIDELINES FOR PROPER ADMINISTRATION

Dissolve the tablet in a little liquid, preferably half a glass of water, and wait until the fizzing or effervescence has stopped. You can stir with a spoon for faster dissolution. Some whitish residue may remain in the glass; if so, add a little more water, stir to dissolve everything, and then drink.

Administration with food : It is recommended to take the medication with food or milk, especially if digestive discomfort is noticed.

Alcoholic beverages should not be consumed during treatment with this medication.

POSOLOGY

- Adults and children 12 years and over: 1 tablet/8-12 h. Maximum dose: 3 tablets (1,200 mg of ibuprofen)/24 h.

Adverse reactions can be minimized by using the lowest effective dose for the shortest time necessary to control symptoms.

- Children < 12 years: not recommended.

- Elderly: may require lower doses (see Precautions).

Duration of treatment : If fever persists for more than 3 days of treatment, pain or other symptoms for more than 5 days, or if the patient's condition worsens or other symptoms appear, the clinical situation should be evaluated. The medication should only be administered when symptoms appear. Treatment should be discontinued as soon as the symptoms disappear.

Dosage in special situations:

- Heart failure:

* Mild to moderate heart failure: reduce the dose, using with caution the lowest possible dose of ibuprofen.

* Severe heart failure (NYHA class IV): the use of ibuprofen is contraindicated.

DOSAGE IN HEPATIC INSUFFICIENCY

- Mild to moderate hepatic impairment (Child-Pugh classes A and B): reduce the dose, using with caution the lowest possible dose of ibuprofen.

- Severe hepatic impairment (Child-Pugh class C): the use of ibuprofen is contraindicated.

DOSAGE IN RENAL INSUFFICIENCY

- Mild to moderate renal impairment (CLcr 30-90 ml/min): reduce the dose, using the lowest possible dose of ibuprofen with caution.

- Severe renal insufficiency (CLcr < 30 ml/min): the use of ibuprofen is contraindicated.

PRECAUTIONS

- Cardiovascular effects. Clinical studies suggest that the use of ibuprofen, particularly at a high dose (≥ 2,400 mg/24 h), may be associated with a small increased risk of arterial thrombotic events (e.g., myocardial infarction or stroke). In general, epidemiological studies do not suggest that low-dose ibuprofen (patients with uncontrolled hypertension, congestive heart failure (NYHA II-III), established ischemic heart disease, peripheral artery disease, and/or cerebrovascular disease (stroke or cerebral ischemia)) should only be treated with ibuprofen after careful consideration, and high doses (≥ 2,400 mg/24 h) should be avoided.

A careful assessment should also be carried out before starting long-term treatment of patients with cardiovascular risk factors: [HYPERTENSION], [DYSLIPIDEMIA], [DIABETES], [SMOKING], especially if high doses of ibuprofen are required (=/> 2,400 mg/24 h).

To avoid the onset of cardiovascular problems, the maximum dose of 1,200 mg/24 h of ibuprofen should not be exceeded.

- Gastrointestinal effects. In patients at risk or who have experienced gastrointestinal disturbances due to the use of NSAIDs, ibuprofen should be administered with caution and under medical supervision; cases of gastroduodenal ulcers, as well as bleeding and perforation, which could be fatal, have been reported. The risk of ulcer is increased with high doses or prolonged treatment, in patients with a history of peptic ulcer, especially if they have already experienced gastrointestinal bleeding or perforation, and in the elderly.

As a general rule, it is advisable to take any NSAID with food to reduce gastric damage. Furthermore, in at-risk groups, it is recommended to start treatment with the lowest possible dose and, whenever possible, to combine it with an anti-ulcer drug (H2 antagonists or proton pump inhibitors).

Those being treated with drugs that may promote bleeding, such as oral anticoagulants or antiplatelet agents, should be closely monitored.

If symptoms of an active ulcer or gastrointestinal bleeding appear, treatment should be discontinued. Likewise, ibuprofen treatment should not be initiated in individuals with an active peptic ulcer (see Contraindications).

- Chronic asthma. Hypersensitivity reactions with bronchospasm are especially common in these patients, so extreme caution is advised. If respiratory function worsens, ibuprofen administration should be discontinued.

[RENAL INSUFFICIENCY]. Ibuprofen elimination may be reduced in cases of renal insufficiency, with a risk of toxicity. Furthermore, it may lead to decreased renal blood flow with reversible acute renal failure, and cases of nephrotic syndrome and acute interstitial nephritis have even been reported with prolonged treatment. In patients with mild to moderate renal insufficiency (creatinine clearance between 30-90 ml/min), it is recommended to initiate treatment with a lower dose than that used in patients with normal renal function, while carefully monitoring the patient. Use in severe renal insufficiency (creatinine clearance < 30 ml/min) is contraindicated (See Contraindications).

- [HEPATIC INSUFFICIENCY]. Due to its hepatic metabolism, accumulation and toxicity may occur in cases of hepatic insufficiency. In patients with mild to moderate hepatic insufficiency (Child-Pugh class A or B), it is recommended to initiate treatment with a lower dose than that used in patients with normal hepatic function, while carefully monitoring the patient. Use in severe hepatic insufficiency (Child-Pugh class C) is contraindicated (See Contraindications).

- [INFLAMMATORY BOWEL DISEASE]. NSAIDs may precipitate symptomatic flare-ups of diseases such as Crohn's disease or ulcerative colitis, so caution is advised when using them, and their use should be avoided in cases of active disease (See Contraindications).

- [ASEPTIC MENINGITIS]. Rare cases of aseptic meningitis have been reported in patients treated with NSAIDs, probably due to a hypersensitivity reaction, although no cross-allergy between NSAIDs has been found. It has been more frequent in patients with [SYSTEMIC LUPUS ERYTHEMATOSUS] and other [COLLAGENOSES], although it has also been reported in some patients without these conditions. In patients treated with NSAIDs who develop symptoms of meningitis, the possibility of aseptic meningitis should be considered.

- Due to the risk of CNS depression, the patient should be advised to avoid consuming alcoholic beverages or ingesting CNS depressants (barbiturates or tranquilizers) together with the medication.

- May produce cross-sensitivity: Patients sensitive to one antihistamine may be sensitive to other antihistamines.

- Patients with pathologies that could be aggravated by anticholinergic or sympathomimetic effects, such as [CONSTIPATION], [INTESTINAL OBSTRUCTION], [HIATAL HERNIA], [GASTROESOPHAGEAL REFLUX DISEASE], stenosing [PEPTIC ULCER], [ULCERATIVE COLITIS], heart failure, [ATHEROSLEROSIS], peripheral artery disease, [ANEURYSM], [PROSTATIC HYPERPLASIA] or other causes of [URINARY RETENTION].

- Situations that could raise body temperature. Anticholinergic drugs could interfere with the body's thermoregulatory capacity, thus potentially increasing the risk of heat stroke in patients exposed to extreme heat, especially the elderly, those who perform intense physical exercise in inappropriate clothing or at inappropriate times, or those undergoing treatment with drugs such as diuretics or others that promote dehydration.

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

- Patients being treated with tricyclic antidepressants or maprotiline or other drugs with anticholinergic action with chlorphenamine should report the appearance of gastrointestinal problems as soon as possible, as paralytic ileus could occur.

PRECAUTIONS RELATING TO EXCIPIENTS

This medicine contains aspartame as an excipient. Aspartame contains a source of phenylalanine, which may be harmful to people with phenylketonuria (PKU), a rare genetic disorder in which phenylalanine builds up because the body is unable to eliminate it properly. 10 mg of aspartame is equivalent to 5.61 mg of phenylalanine.