SPIDIDOL 400 MG 20 ENVELOPES GRANULATED ORAL SOLUTION MINT

- Analgesic, anti-inflammatory, antipyretic. Ibuprofen is a derivative of propionic acid, with anti-inflammatory, analgesic and antipyretic activity. Its mechanisms of action could be due to inhibition of peripheral synthesis of prostaglandins due to their competitive and reversible binding to the enzyme cyclooxygenase, an enzyme that transforms arachydonic acid into such prostaglandins.

- Gastrointestinal risk: NSAIDs are associated with an increased risk of gastrointestinal irritation, ulceration, bleeding or gastrointestinal perforation. Injuries may occur at any time during treatment. The elderly have an increased risk of severe gastrointestinal events. During prolonged treatments, possible signs and symptoms of ulceration or bleeding should be monitored. A history of esophagitis, gastritis and/or peptic ulcer should also be sought to ensure full healing before starting EDV treatment.

- Cardiovascular risk: NSAIDs are associated with an increased risk of cardiovascular events, including myocardial infarction and new cases of hypertension or worsening of existing ones. The risk may be increased with the duration of treatment, especially in patients with cardiovascular disease or with risk factors for cardiovascular disease. Monitor possible signs of hydrosaline retention (e.g. edema formation), especially in patients with hypertension or heart failure.

The elderly appear to be more susceptible to the adverse effects of NSAIDs. The risk of severe ulcerative disease is increased in over 65 years, and appears to be dose-dependent. They can also cause fluid retention, which can lead to cardiovascular complications and reduced effectiveness of antihypertensive treatments. It is recommended to use with caution, using the lowest possible effective dose.

- The patient should inform his doctor in case of skin rashes, symptoms that may be related to a gastroduodenal ulcer (such as epigastric pain or dark stools), visual disturbances, weight gain, edema or prolonged headache.

- The patient should notify the doctor if he or she has had any asthma reactions while taking this medicine.

- Hypersensitivity to ibuprofen or any component of the medicine. Cases of cross hypersensitivity reactions with other NSAIDs have been reported, so it should also not be used in case of [SALICILATOS ALLERGY] or [INE ALLERGY]. These allergic reactions are especially common in asthmatic patients, nasal polyps or who have experienced rhinitis, angioedema or hives when receiving another NSAID or salicylates.

- [PEPTICA ULCERA] active or relapsed, active inflammatory bowel disease or any other process that increases the risk of [GASTROINTESTINAL HEMORRAGIA]. Ibuprofen has ulcerogenic effects due to inhibition of prostaglandin synthesis, so it could increase the risk of digestive bleeding and perforation.

- [COAGULATION ALTERATIONS]. Ibuprofen has antiplatelet effects, although less potent and long lasting than those of aspirin. Therefore, it may increase bleeding time, so it should be used with caution in patients with [HEMORRAGIC DIATESIS] or active [HEMORRAGIA], as well as in patients with [TROMBOCITOPENIA].

- Perioperative pain in the framework of a coronary bypass.

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

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

- Severe heart failure (NYHA class III-IV) or uncontrolled high blood pressure. Fluid retention could worsen these pathologies.

- Pregnancy. Its use is contraindicated during the third trimester of pregnancy, not advising its use for extended periods of time in the first two trimesters.

Patients who experience dizziness, vertigo, visual disturbances or other central nervous system disorders while taking ibuprofen should refrain from driving or operating machinery. No special precautions are usually required for short treatments.

Animal safety: No teratogenic effects have been reported, but foetal damage has been reported on important occasions, as well as involvement of childbirth.

Human safety: there are no adequate and well-controlled human studies. Inhibition of fetal prostaglandin synthesis during the first two gestational trimesters has been associated with an increased risk of abortion, cardiac malformations (up to 1.5% more than placebo) and gastroschisis. The risk appears to be increased with high doses and prolonged treatments.

On the other hand, chronic use during the third trimester could theoretically result in premature closure of the fetal arterious ductus and fetal renal dysfunction at risk of oligohydroamniosis. In addition, due to its antiplatelet effects, bleeding time may be prolonged, with possible fetal involvement and risks in childbirth. Another possible effect that could occur is the reduction and even cancellation of uterine contractility, causing an abnormal delay in childbirth and a non-physiological prolongation of gestation.

It is not known whether timely administration of an NSAID could pose a fetal risk.

The use of ibuprofen during the first two trimesters of pregnancy is only accepted in the event that there are no safer therapeutic alternatives, the benefits outweigh the potential risks. If used, it will be done at the lowest possible dose and for the shortest possible time. The use of an NSAID in the third trimester is contraindicated.

Oral, parenteral route:

Acid ibuprofen is a racemic compound, of which S(+)-enantiomer possesses almost all pharmacological activity. In vivo, almost 70% of the R(-)-enantiomer of ibuprofen acid is converted into the S(+)-enantiomer, pharmacologically active.

Linear pharmacokinetics in the dosage range of 200-800 mg

- Absorption:

- Treatment of [PAIN] from mild to moderate.

- NSAIDs, including low doses of aspirin: simultaneous use of more than one NSAID should be avoided by the risk of adverse effects without increasing therapeutic efficacy. In addition, ibuprofen may reduce the antiplatelet efficacy of aspirin when administered together. If both drugs are needed, it is advised to distance the intakes (administer ibuprofen 8 hours before or 30 minutes after AAS).

- Alcohol: toxicity can be enhanced.

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

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

- Quinolonic antibacterials: there are isolated reports of seizures that may have been due to concomitant use of quinolone and SOME nonsteroidal anti-inflammatory drugs.

- Oral anticoagulants, heparin: possible increase of anticoagulant effect, with risk of bleeding. Periodic checks of coagulation rates are recommended.

- Antidiabetic sulphonylureas (chlorpropamide, glibenclamide, tolbutamide): possible increase in hypoglycaemic effects, by reducing renal excretion.

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

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

- Oral bisphosphonates (alendronic acid): possible increased risk of esophagitis and gastric ulcer. Described cases with naproxen and alendronate.

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

- Antiplatelet agents, including pentoxyphline: there is an increased risk of bleeding in general, and gastrointestinal 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 reduce glycocorticoid dosage.

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

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

- Potassium-saving diuretics and aldosterone antagonists: possible increase in the risk of hyperkalaemia. Frequent monitoring of serum potassium levels is recommended.

- Glitazones (pioglitazone, rosiglitazone): theoretical risk of edema empowerment that both glitazones and NSAIDs can cause. Caution and monitor possible signs of fluid retention and heart failure (swollen ankles, dyspnoea).

- Hydralozine: possible decrease of the hypotensive effect.

- Iloprost: possible increase in the risk of bleeding.

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

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

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

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

- Pentoxyphline: In patients receiving ibuprofen treatment in combination with pentoxyphline may increase the risk of bleeding, so it is recommended to monitor bleeding time.

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

- Ticlopidine: possible increase in the risk of bleeding.

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

After ingestion of 400 mg ibuprofen, no detectable concentrations in breast milk have been detected, with a detection limit of 0.5-1 mcg/ml. However, manufacturers advise not to use it during lactation, due to the risk of inhibiting cyclooxygenase in the infant.

Safety and efficacy in children under 3 months of age have not been established, so their use is not recommended. Ibuprofen should not be self-medicated to children under 12 years of age.

Food administration :administered together with food.

- Mild to moderate hepatic impairment (Child-Pugh classes A and B): use with caution at the lowest possible dose.

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

- Mild to moderate renal impairment (CLcr 30-90 ml/min): use with caution at the lowest possible dose.

- Severe renal impairment (CLcr < 30 ml/min): contraindicated.

- [RENAL INSUFFICIENCY]. Ibuprofen is removed by urine, so in case of kidney failure accumulation may occur, at risk of poisoning. In addition, it could lead to a decrease in renal blood flow with reversible acute renal failure due to inhibition of vasodilating prostaglandin synthesis, and cases of nephrotic syndrome and acute interstitial nephritis have even been reported with prolonged treatments. In patients with mild to moderate impairment (CLcr between 30-90 ml/min) it is recommended to start treatment at a lower dose than patients with normal renal functionality, carefully monitoring the patient. Use in severe insufficiency (CLcr < 30 ml/min) is contraindicated (see Contraindications).

- [HEPATIC INSUFFICIENCY]. Due to its liver metabolism, accumulation and poisoning may occur in case of hepatic impairment. In patients with mild to moderate impairment (Child-Pugh class A or B) it is recommended to start treatment at a lower dose than patients with normal hepatic function, carefully monitoring the patient. Use in severe insufficiency (Child-Pugh Class C) is contraindicated (see Contraindications).

- History of peptic ulcer. The use of an NSAID, including ibuprofen, has resulted in tables of gastroduodenal ulcers, as well as bleeding and cases of perforation that could be fatal. The risk of ulceration is increased in treatments at high doses or for long periods of time, patients with a history of peptic ulcer, especially if they have already had bleeding or gastrointestinal perforation, as well as in the elderly.

As a general rule, it is advised to administer any NSAIDs with food, to reduce gastric damage. In addition, in risk groups it is advised to start treatment with the minimum possible dose, and to associate whenever possible an antiulcer drug (H2 antihistamines or pump inhibitors).

These patients, as well as those receiving drugs that may promote bleeding, such as oral anticoagulants or antiplatelet agents, should be closely monitored.

If symptoms of active ulcer or digestive bleeding occur, treatment will be discontinued. Similarly, ibuprofen treatment should not be initiated in people with active peptic ulcer (see Contraindications).

- [INTESTINAL INFLAMMATORY DISEASE]. NSAIDs could precipitate symptomatic seizures of diseases such as Crohn's disease or ulcerative colitis, so it is advised to use it with caution, and avoid its use in case of active diseases (see Contraindications).

- Cardiovascular effects. NSAIDs may result in fluid retention (especially with prolonged use), due to inhibition of vasodilating prostaglandin synthesis, which could result in the onset or aggravation of [ARTERIAL HIPERTENSION], especially in cases where prior treatment does not exist, or where the disease has not been able to control the disease.

On the other hand, the administration of high doses of ibuprofen (A/> 2,400 mg/24 h) has been linked to increased risk of arterial thrombosis, similar to that of specific COX-2 inhibitors at therapeutic doses. Therefore, it is recommended to avoid the use of these doses in patients with moderate to severe [CARDIACA INSUFFICIENCY] (NYHA Classes II-IV), [ISQUEMICA CARDIOPATIA], [ARTERIOPATIA PERIFERICA], [ICTUS] or [CEREBRAL ISQUEMIA].

Before starting long-term treatment with ibuprofen, and especially if high doses are needed, it would be advisable to evaluate other cardiovascular risk factors such as [DISLIPEMIA], [DIABETES] or [TABAQUISMO].

The use of reduced doses of ibuprofen (1,200 mg/24 h) and for a limited period of time does not appear to present the same cardiovascular risks. Therefore, as with other NSAIDs, the general recommendation would be to use it at the minimum dose to control symptoms and for the shortest possible period of time.

- Skin reactions. The use of NSAIDs has caused very rare but life-threatening serious adverse reactions, such as exfoliative dermatitis, toxic epidermal necrolysis or Stevens-Johnson syndrome. These adverse reactions are usually early onset in the first month of treatment. If symptoms of hypersensitivity, mucous lesions or skin erythema are found, treatment will be discontinued.

- Chronic [ASMA]. In these patients, hypersensitivity reactions with bronchospasm are especially common, so extreme precautions are recommended. If worsening of respiratory function is observed, treatment will be discontinued.

- [MENINGITIS ASEPTICA]. Rare cases of aseptic meningitis have been reported in patients treated with NSAIDs, probably due to a hypersensitivity reaction, although no cross-allergy has been found between NSAIDs. It has been more common in patients with [LUPUS ERITEMATOSO SISTEMICO] and others [COLAGENOSIS], although it has also been reported in some patients who did not have these pathologies. In patients treated with NSAIDs who develop symptoms of meningitis, the possibility of aseptic meningitis should be considered.

- Ibuprofen lysine is contraindicated in case of infection or suspected infection in preterm children.

- This medicine contains aspartame as an excipient, so it should be taken into account by those affected by [FENILCETONURIA]. 100 mg aspartame corresponds to 56.13 mg phenylalanine.

Adverse reactions are more common at doses of 3200 mg/day.

- Gastrointestinal: (>10%): [DISPEPSIA], [DIARREA]. (1-10%): [NAUSEAS], [VOMITOS], [ABDOMINAL PAIN]. (0.1-1%): [GASTROINTESTINAL HEMORRHAGE], [GASTRIC ULCER], [DUODENAL ULCER], [ORAL CANKER SORES]. (<0.1%): [INTESTINAL PERFORATION], [FLATULENCE], [STRESS], [ESOFAGITIS], [ESOFAGICAL OBSTRUCTION], exacerbation of diverticular disease, non-specific hemorrhagic colitis, [ULCERATIVE COLITIS] or [CROHN'S DISEASE], [MELENA]. If gastrointestinal bleeding occurs, it could cause anemia and [HEMATEMESIS].

- Dermatological/Hypersensitivity: (1-10%): [EXANTEMATIC ERUPTIONS]. (0.1-1%): [URTICARIA], [PRURITO], [PURPURA] (including allergic purple), [ANGIOEDEMA], [RINITIS], [BRONQUIAL SPASM]. (<0.1%): [ANAFILAXIA]. (<0.01%): [ERYTHEMA MULTIFORME], [TOXIC EPIDERMIC NECROLISIS], systemic lupus erythematosus, [ALOPECIA], [PHOTOSENSITIVITY REACTIONS], severe skin reactions such as [STEVENS-JOHNSON SYNDROME], [TOXIC EPIDERMIC NECROLYSIS] (Lyell syndrome) and allergic [VASCULITIS] ; unknown frequency [SINDROME DRESS] (which may include rash, inflammation of the lymph nodes and [EOSINOFILIA]).

In most cases where [MENINGITIS ASEPTICA] has been reported with ibuprofen, the patient suffered from some form of autoimmune disease (such as systemic lupus erythematosus or other collagen diseases) which was a risk factor. It is manifested by severe headache, nausea, vomiting, fever, stiff neck and some obnubilation, possibly due to a hypersensitivity reaction. An increase in intrathecal synthesis of IgG has been observed, with the presence of immunocomplejos in cerebrospinal fluid.

Anaphylactic or anaphylaid reactions typically occur in patients with a history of hypersensitivity to aspirin and other nonsteroidal anti-inflammatory drugs. This could also happen in patients who have not previously shown hypersensitivity to these drugs.

In case of severe generalized hypersensitivity reaction, swelling of the face, tongue and larynx, bronchospasm, asthma, tachycardia, hypotension and shock may occur.

- Central nervous system: (1-10%): [ASTENIA], [SOMNOLENCIA], [CEFALEA], [MAREO], [VERTIGO]. (0.1-1%): [INSOMNIA], [ANXIETY]. (<0.1%): [PSICOSIS], [NERVIOSISMO], [IRRITABILITY], [DEPRESION], [CONFUSION] or disorientation reaction.

- Haematological: May prolong bleeding time. The rare observed cases of haematological disorders correspond to [TROMBOCITOPENIA], [LEUCOPENIA], [GRANULOCITOPENIA], [PANCITOPENIA], [AGRANULOCITOSIS], [APLASICA ANAEMIA], [HEMOLITIC ANAEMIA].

- Cardiovascular: There appears to be a greater predisposition on the part of patients with hypertension or renal disorders to suffer [EDEMA]. [ARTERIAL HYPERTENSITENSION] or [CARDIAC INSUFFICIENCY] (especially in elderly patients) may occur.

- Renals: [UREIC NITROGEN INCREASE] and [SERICA CREATININE INCREASE]. In exceptional cases, NSA May Be Responsible for [ACUTE RENAL INSUFFICIENCY], [INTERSTITIAL NEPHRITIS], [GLOMERULONEFRITIS], [RENAL MEDULAR NECROSIS] or [NEPHROTIC SINDROME], [PROTEINURIA], [HIPERPOTASEMIA], [HIPOPOTASEMIA] and edema. It has been observed in susceptible patients taking high doses of NSAIDs for extended periods of time. It is at-risk patients who have heart, renal or hepatic impairment, ascites, hyperreninemia, hyperaldosteronemia, shock, sepsis, systemic lupus erythematosus, dehydration, those treated with IECA or diuretics and the elderly.

- Hepatic: In rare cases [INCREASE OF TRANSAMINASAS], [HEPATITIS] and [ICTERICIA] have been observed.

- Otological: Rarely, [TINNITUS].

- Ophthalmics: Optical reactions such as [VISION BORROSA], decreased visual acuity or changes in color perception ([DISCROMATOPSIA]) have very rarely been observed after administration of ibuprofen, which they spontaneously refer. Isolated cases of reversible toxic [AMBLIOPIA].

- Inflammations associated with infections may be aggravated in very rare cases.

Symptoms: Ibuprofen can result in toxic effects from doses of 80-100 mg/kg, with symptoms appearing within about 4 hours. In case of mild overdose symptoms such as abdominal pain, nausea and vomiting, headache, drowsiness, lethargy, nistagmus, tinnitus and ataxia may occur. More severe symptoms rarely appear, although digestive bleeding, hypotension, hypothermia, metabolic acidosis, seizures, kidney failure, coma, adult respiratory distress and transient apnea may occur in children after ingesting large amounts.

Treatment: There is no specific antidote.

In the event of mild overdose, per dose of up to 50 mg/kg, which is not expected to result in symptomatic poisoning, water will be administered to mitigate possible gastrointestinal reactions.

In case of major overdose, and if less than an hour has elapsed, the elimination of unin absorbed ibuprofen by administration of active carbon and forced emesis shall be encouraged. Forced emesis is contraindicated in children who have ingested more than 400 mg/kg due to the risk of seizures and aspiration pneumonia. Gastric lavage is only recommended for overdoses that could be potentially fatal.

If more than an hour of overdose has passed, symptomatic treatment will be instituted, especially in the face of hypotension, digestive bleeding and metabolic acidosis. Forced diuresis may be attempted with urine alkalinization.

Due to its high plasma protein binding, ibuprofen is not expected to be eliminated by haemodialysis.