Ibudol 400 Mg 20 Envelopes Oral Suspension 10 Ml

Ibudol (400 Mg 20 Envelopes Oral Suspension 10 Ml)

ACTION AND MECHANISM

- 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 the inhibition of peripheral synthesis of prostaglandins due to their competitive and reversible binding to the enzyme cyclooxygenase, an enzyme that transforms arachidonic acid into these prostaglandins.

PHARMACKINETICS

Oral, parenteral route:

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

Linear pharmacokinetics in the dosage range of 200-800 mg

- Absorption:

* Oral administration: good and rapid oral absorption, with a bioavailability of 80% and a tmax of 1-3 h, depending on the pharmaceutical form (47 min in suspension, 120 min in tablets). Arginine and lysine salts favor the solubilization of ibuprofen, so it is absorbed even more quickly, with a tmax of 20-30 min. After administration of a dose of 200 mg the cmax is 15-20 mcg / ml.

The antipyretic effects begin after one hour, are maximum at 2-4 h, and can be prolonged for periods of 6-8 h.

For its part, to achieve anti-inflammatory effects may require up to 2 weeks of treatment.

Food effect : delay absorption about 30-60 min and cmax 30-50%, although they do not affect the total amount absorbed.

- Distribution: high plasma protein binding (90-99%). You of 0.1-0.2 l / kg. Ibuprofen diffuses well, passes into synovial fluid and crosses the placental barrier. It has not been detected in the milk of lactating women (detection limit 0.5 mcg / ml).

- Metabolism: extensively metabolized in the liver by hydroxylation and carboxylation of the isobutyl group, generating several inactive metabolites, of which the majority are 2- [4- (2-hydroxy-2-methyl-propyl) -phenyl] propionic acid and 2- [4- (carboxypropyl) -phenyl] propionic acid

- Excretion: in urine (90%; 50-60% major metabolites and their glucuronides and <10% unchanged), with minor amounts in feces. The t1 / 2 is 2-4 h, and its elimination is complete at 24 h.

Pharmacokinetics in special situations :

- Children: Although the distribution and t1 / 2 appear similar to those of adults, the ibuprofen CLt could be affected by age.

- Renal impairment: in mild insufficiency (CLcr 60-90 ml / min) there is an increase in the free fraction (3%), an increase in AUC and the ratio of the S / R enantiomers. The elimination of metabolites could be reduced in patients with more severe renal impairment.

- Hepatic impairment: in moderate insufficiency (Child-Pugh class B) t1 / 2 doubled while reducing the ratio of S / R enantiomers, which would indicate the difficulty of converting the R enantiomer into the active form.

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INDICATIONS

- Treatment of [PAIN] of mild to moderate.

- Symptomatic treatment of [FEVER].

POSOLOGY

- Adults: 400 mg / 6-8 h. Maximum dose 1,200 mg / 24 h.

- Children and adolescents <18 years:

* Adolescents from 12 years (> 40 kg): 400 mg / 6-8 h. Maximum dose 1,200 mg / 24 h.

* Children <12 years (<40 kg): use presentations adapted to this age.

- Elderly: may require a dose reduction.

Food administration: administer with food.

Duration of treatment : consult with the doctor and / or pharmacist in case of worsening of symptoms or persistence for more than 5 days (pain) or 3 days (fever).

Missed dose : administer the next dose at the usual time. Do not double the next dose.

POSOLOGY IN RENAL INSUFFICIENCY

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

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

POSOLOGY IN HEPATIC INSUFFICIENCY

- 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.

RULES FOR THE CORRECT ADMINISTRATION

Food administration: administer with food.

- Oral suspension envelopes: press the envelope with your fingers to homogenize its contents, and then drink directly or dilute the suspension in water.

CONTRAINDICATIONS

- Hypersensitivity to ibuprofen or any component of the medication. Cases of cross-hypersensitivity reactions with other NSAIDs have been described, so it should not be used in the case of [ALICIIA A SALICILATOS] or [ALERGIA A NSAID]. These allergic reactions are especially frequent in asthmatic patients, with nasal polyps or who have experienced rhinitis, angioedema or urticaria when receiving another NSAID or salicylates.

- [PEPTIC ULCERA] active or recurrent, active inflammatory bowel disease or any other process that increases the risk of [GASTROINTESTINAL HEMORRAGY]. Ibuprofen has ulcerogenic effects due to the inhibition of prostaglandin synthesis, which could increase the risk of gastrointestinal bleeding and perforation.

- [COAGULATION CHANGES]. Ibuprofen has platelet antiaggregant effects, although less potent and long lasting than those of acetylsalicylic acid. Therefore, the bleeding time can be increased, so it should be used with caution in patients with [HEMORRAGICAL DIATESIS] or [HEMORRAGY] active, as well as in patients with [THROMBOCYTOPENIA].

- 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 arterial hypertension. Fluid retention could worsen these pathologies.

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

PRECAUTIONS

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

- [LIVER FAILURE]. Due to his hepatic metabolism, in case of hepatic insufficiency accumulation and poisoning could occur. In patients with mild to moderate insufficiency (Child-Pugh class A or B) it is recommended to start treatment with a dose lower than that of patients with normal liver 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 cases of gastroduodenal ulcers, as well as bleeding and perforation cases that could be fatal. The risk of ulcer is increased in high-dose treatments or for long periods of time, patients with a history of peptic ulcer, especially if they have already had gastrointestinal bleeding or perforation, as well as in the elderly.

As a general rule, it is advisable to administer any NSAID with food, to reduce gastric damage. In addition, in risk groups it is advisable to start the treatment with the minimum possible dose, and to associate whenever possible an antiulcer drug (h3 antihistamines or pump inhibitors).

These patients should be closely monitored, as well as those who are being treated with drugs that may favor bleeding, such as oral anticoagulants or platelet antiaggregants.

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

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

- Cardiovascular effects. NSAIDs could lead to fluid retention (especially with prolonged use), due to inhibition of vasodilatory prostaglandin synthesis, which could lead to the appearance or aggravation of [ARTERIAL HYPERTENSION], especially in cases where that there is no previous treatment, or in those who have not been able to control the disease.

On the other hand, the administration of high doses of ibuprofen (= /> 2,400 mg / 24 h) has been associated with an 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 [CARDIAC INSUFFICIENCY] (NYHA classes II-IV), [ISCHEMICAL CARDIOPATIA], [PERIPHERAL ARTERIOPATIA], [ICTUS] or [CEREBRAL ISCHEMIA].

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 [DYSLIPEMIA], [DIABETES] or [SMOKING].

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

- Skin reactions. The use of NSAIDs has caused very rare but potentially fatal 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 cutaneous erythema are observed, the treatment will be suspended.

- [ASTHMA] chronic. In these patients the occurrence of hypersensitivity reactions with bronchospasm is especially frequent, so it is recommended to exercise caution. If worsening of respiratory function is observed, treatment will be suspended.

- [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 has been found among NSAIDs. It has been more frequent in patients with [SYSTEM ERYTHEMATOSUS LUPUS] and others [COLAGENOSIS], although it has also been notified in some patients who did not suffer from 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 suspicion of it in preterm children.

PRECAUTIONS RELATING TO EXCIPIENTS

- This medicine contains sodium salts. To know the exact sodium content, it is recommended to check the composition. Oral and parenteral dosage forms with sodium amounts greater than 1 mmol (23 mg) / maximum daily dose should be used with caution in patients with [RENAL INSUFFICIENCY] or with low sodium diets.

- This medicine contains maltitol. Patients with hereditary [INTOLERANCE TO FRUCTOSE] should not take this medication.

PATIENT ADVICE

- The patient should inform their doctor if they experience skin rashes, symptoms that could be related to a gastroduodenal ulcer (such as epigastric pain or dark stool), visual disturbances, weight gain, edema or prolonged headache.

- The patient should notify the doctor if he has had any asthmatic reaction while taking this medication.

SPECIAL WARNINGS

- Gastrointestinal risk: NSAIDs are associated with an increased risk of gastrointestinal irritation, ulceration, bleeding or gastrointestinal perforation. Lesions may appear at any time during treatment. The elderly have a higher risk of serious 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 complete healing before starting treatment with an NSAID.

- 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 increase with the duration of treatment, especially in patients with cardiovascular disease or with risk factors for cardiovascular disease. Monitor possible signs of hydrosaline retention (eg, formation of edema), especially in patients with hypertension or heart failure.

INTERACTIONS

- NSAIDs, including low doses of acetylsalicylic acid: the simultaneous use of more than one NSAID should be avoided due to the risk of adverse effects without increasing therapeutic efficacy. In addition, ibuprofen may reduce the antiaggregant efficacy of acetylsalicylic acid when co-administered. If the administration of both drugs is needed, it is advisable to distance the doses (administer ibuprofen 8 hours before or 30 minutes after ASA).

- 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), deterioration of 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 h on an empty stomach to ± 3 h after taking food), although this has no effect on absorbed amount.

- Quinolonic 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 anticoagulant effect, with risk of bleeding. Periodic checks of coagulation rates are advised.

- Sulfonylureas antidiabetics (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 in particular, especially in the elderly and patients with a history of gastrointestinal bleeding.

- Antihypertensives (ACEI, 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.

- Platelet antiaggregants, including pentoxifylline: there is an increased risk of bleeding in general, and gastrointestinal in particular. Manage 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 the dosage of glucocorticoid.

- Digitálicos (digoxina): possible of increase of the digital concentrations of the digitalálico (in neonates). There is also a risk of worsening heart failure and reduced renal function.

- Diuretics (thiazides, high ceiling diuretics): risk of reducing the natriuretic and diuretic effect. It can 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 that both glitazones and NSAIDs can cause. Caution and monitor possible signs of fluid retention and heart failure (swollen ankles, dyspnea).

- Hydralazine: possible decrease of the hypotensive effect.

- Iloprost: possible increased risk of bleeding.

- Lithium, salts: possible by 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 methotrexate levels, with risk of toxicity, sometimes very serious. The severity depends largely 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: Non-steroidal anti-inflammatories should not be administered within 8-12 days after the administration of mifepristone as these may reduce the effects of it.

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

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

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

- Ticlopidine: possible increased risk of bleeding.

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

PREGNANCY

Safety in animals: no teratogenic effects have been recorded, but fetal damage has been reported on important occasions, as well as childbirth involvement.

Safety in humans: there are no adequate and well-controlled studies in humans. 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 with placebo) and gastroschisis. The risk seems to increase with high doses and prolonged treatments.

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

It is unknown whether the timely administration of an NSAID could pose a fetal risk.

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

Fertility effects: Ibuprofen may alter female fertility and is not recommended in women who are trying to conceive. In women with difficulties in conceiving or who are undergoing fertility research, the suspension of this medication should be considered.

LACTATION

After ingestion of 400 mg of ibuprofen, no detectable concentrations have been detected in breast milk, with a detection limit of 0.5-1 mcg / ml. However, manufacturers advise against using during breastfeeding, due to the risk of inhibiting cyclooxygenase in infants.

CHILDREN

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

ELDERLY

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

EFFECTS ON DRIVING

Patients who experience dizziness, vertigo, visual disturbances or other disorders of the central nervous system while taking ibuprofen should refrain from driving or operating machinery. Generally short treatments do not require special precautions.

ADVERSE REACTIONS

Adverse reactions are more frequent with doses of 3200 mg / day.

- Gastrointestinal: (> 10%): [Dyspepsia], [DIARRHEA]. (1-10%): [NAUSEAS], [VOMITOS], [ABDOMINAL PAIN]. (0.1-1%): [GASTROINTESTINAL HEMORRAGY], [GASTRIC ULCERA], [DUODENAL ULCERA], [ORAL AFTAS]. (<0.1%): [INTESTINAL PERFORATION], [FLATULENCE], [CONSTIPATION], [ESOFAGITIS], [ESOFAGIC OBSTRUCTION], exacerbation of diverticular disease, nonspecific hemorrhagic colitis, [ULCEROSA 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 purpura), [ANGIOEDEMA], [RHINITIS], [BRONCHIAL SPASM]. (<0.1%): [ANAFILAXIA]. (<0.01%): [MULTIFORM ERYTHEMA], [TOXIC EPIDERMIC NECROLYSIS], systemic lupus erythematosus, [ALOPECIA], [PHOTOSENSITIVITY REACTIONS], severe skin reactions such as [STEVENS-JOHNSON SYNDROME], [EPIDERMICAIC EPIDERMICAIS SYNDROXIS] Lyell) and allergic [VASCULITIS]; unknown frequency [SYNDROME DRESS] (which may include rash, swollen lymph nodes and [EOSINOPHILY]).

In most of the cases in which [ASEPTIC MENINGITIS] 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 immune complexes in the cerebrospinal fluid.

Anaphylactic or anaphylactoid reactions normally occur in patients with a history of hypersensitivity to acetylsalicylic acid and other nonsteroidal anti-inflammatory drugs. This could also happen in patients who have not prev