Spedifen

Ibuprofen arginine.

Each tablet also contains the following excipients: Sodium hydrogen carbonate, crospovidone, magnesium stearate, hypermellose, sucrose, titanium dioxide and macrogol 4000.

Pharmacology: Pharmacodynamics: Ibuprofen is an analgesic-anti-inflammatory drug, also endowed with antipyretic properties. It is a phenylpropionic acid derivative and its analgesic action is not of narcotic type. Its pharmacological activity is based on the prostaglandin synthesis inhibition at peripheral level.
Pharmacokinetics: Spedifen allows a high and prompt ibuprofen absorption, due to the presence of the amino acid L-arginine, that favors its solubilization and improves its bioavailability, thus reaching plasma concentration peaks 20 min after administration. Spedifen administration did not show evidence of accumulation phenomena, both for ibuprofen arginine and its metabolites. Its plasma half-life is 2 hrs and the drug excretion is practically complete 24 hrs after last administration.
Toxicology: Preclinical Safety Data: In some reproduction studies on animals, an increase in dystocia and labor delay were observed, which are related to prostaglandin synthesis inhibition induced by nonsteroidal anti-inflammatory drugs.

Relief of pain of various etiology: Headache, pain after tooth extraction and postoperative pain. Treatment of primary dysmenorrhea.
Relief of signs and symptoms of rheumatoid arthritis and osteoarthritis, as well as for the musculoskeletal and traumatic alterations implying pain and inflammation.

Adults: Recommended Dose: 1200 mg/day divided into 3-4 single administrations. Should gastric disturbances appear after ingestion of Spedifen, then the administration can be performed by drinking concomitantly some milk or during meals.
Rheumatoid Arthritis: A higher dosage may be required but in any case, it is recommended not to exceed ibuprofen 2400 mg/day, by considering that the lowest possible effective dose is to be administered.
Primary Dysmenorrhea: Recommended Dose: 400 mg every 4 hrs until pain relief, always considering the lowest possible effective dosage.
Elderly: The dosage is to be established by the physician, as a possible usual dose reduction may be needed.
Kidney Failure: Dosage must be adequately adjusted, being the drug eliminated preferably through renal excretion.

In case of overdosage, whose symptoms may include dizziness, spasms, hypotension and conscience reduction, a gastrolavage is recommended if <1 hr has passed. The support of substances by oral route eg, active charcoal, can be useful to reduce the absorption of Spedifen. If >1 hr has passed from the excessive ingestion, it is recommended to adjust the hematic electrolytes by adding alkalies, as no specific antidote for ibuprofen is available.

Hypersensitivity to ibuprofen. Active and recurrent peptic ulcer or risk of gastrointestinal hemorrhage, ulcerative colitis, serious liver and/or kidney failure.
Owing to a possible crossed allergic reaction with acetylsalicylic acid and other nonsteroidal anti-inflammatory drugs (NSAIDs), ibuprofen must not be administered in patients with history of allergic reactions to medicines alike eg, asthma, rhinitis, urticaria, nasal polyps and angioedema.
Spedifen is contraindicated for the treatment of perioperative pain in the setting of coronary artery bypass graft (CABG) surgery.

Cardiovascular Risk: NSAIDs may cause an increased risk of serious cardiovascular thrombotic events, myocardial infarction and stroke, which can be fatal. This risk may increase with duration of use. Patients with cardiovascular disease or risk factors for cardiovascular disease may be at greater risk.
Gastrointestinal Risk: NSAIDs cause an increased risk of serious gastrointestinal adverse events including bleeding, ulceration and perforation of the stomach or intestines, which can be fatal. These events can occur at any time during use and without warning symptoms. Elderly patients are at greater risk for serious gastrointestinal events.

In patients at risk or who reported gastrointestinal alterations due to the use of NSAIDs, ibuprofen must be administered with due caution and under medical surveillance. Similarly, it must be used with caution in patients with history of bronchospasm following the use of other drugs, as well as in elderly patients and in patients with reduced renal, hepatic and/or cardiac function. For all these subjects, a periodic monitoring of clinical and laboratory parameters is required, especially in case of long-term treatment.
In some cases, water retention after ibuprofen administration was observed; thus, Spedifen must be used with caution in patients with heart failure and hypertension. Ibuprofen, similarly to other NSAIDs, can prolong the bleeding time, thus it must be used with due caution in patients with blood coagulation alterations or undergoing an anticoagulant treatment.
In case of previous treatment with corticosteroids, it is recommended to adjust gradually their dosage if an ibuprofen-combined therapy is to be performed.
Only seldom, aseptic meningitis in patients under treatment with ibuprofen was observed. Although this effect is more probably reported in patients with systemic lupus erythematosus and other collagen diseases, it was also observed in some patients who did not suffer from any chronic disease. This feature must be duly considered in case of drug administration.
Ophthalmologic alterations, though of rare occurrence, were observed (see Adverse Reactions). In this case, it is recommended as precautionary measure to discontinue the treatment and perform an ophthalmologic examination.
Similarly to other NSAIDs, some cases of acute interstitial nephritis with hematuria, dysuria and occasionally, nephrotic syndrome were observed after prolonged treatment with ibuprofen.
Anaphylactic reactions may occur when IV acetylcysteine is directly administered at high doses as well as when very fast rate is used. Treatment of those reactions must be symptomatic. Therefore, Hidonac must be administered as described in Dosage & Administration. Patients suffering from bronchial asthma or with a history of asthma must be closely controlled since bronchospasm may occur during treatment. In such event, the treatment must be immediately suspended. Intravenous administration must be done in a hospital under strict medical surveillance.
Effects on the Ability to Drive or Operate Machinery: Ibuprofen must be used with due caution in patients whose activity requires particular attention and who complained about somnolence, dizziness or depression during treatment with Spedifen.
Use in pregnancy: Although studies performed in animals did not show evidence of teratogenic action, it is recommended to avoid ibuprofen administration during the 1st months of pregnancy, as these studies are not predictive of a certain human response. Similarly, owing to prostaglandin synthesis inhibition and some cases, to fetal cardiovascular effects (closing of Botallo's duct), it is recommended not to administer ibuprofen during the last months of pregnancy, except in cases of strict necessity.
Use in lactation: Being proved the passage of ibuprofen into the mother's milk, its administration is not recommended during the lactation period.

Use in pregnancy: Although studies performed in animals did not show evidence of teratogenic action, it is recommended to avoid ibuprofen administration during the 1st months of pregnancy, as these studies are not predictive of a certain human response. Similarly, owing to prostaglandin synthesis inhibition and some cases, to fetal cardiovascular effects (closing of Botallo's duct), it is recommended not to administer ibuprofen during the last months of pregnancy, except in cases of strict necessity.
Use in lactation: Being proved the passage of ibuprofen into the mother's milk, its administration is not recommended during the lactation period.

At gastrointestinal level, nausea, vomiting, dyspepsia, gastric pyrosis, abdominal pain, diarrhea, intestinal microlesions, possible ulcerative activation and hemorrhages can be observed.
Occasionally, headache, confusion, tinnitus and somnolence may appear. Seldom, psychotic reactions and depression, as well as intense headache, nausea, vomiting, fever, neck rigidity and a certain obnubilation were reported. Only rarely, visual disturbances eg, blurred vision, scotoma or altered color perception were observed after ibuprofen administration. These effects however regressed spontaneously.
In terms of hypersensitivity reactions, rash, urticaria and exanthema with or without itching were observed and sometimes, also fever associated with rash, abdominal pain, headache, nausea and vomiting; signs of hepatic dysfunction and anaphylactic phenomena were reported. Only in seldom cases that ibuprofen can induce bronchospasm in predisposed patients.
After prolonged administration at high doses, ibuprofen could induce alterations of the blood corpuscular elements as well as water retention, with the possible onset of swellings and edemas.
In case of onset of adverse events, the treatment must be suspended.

Ibuprofen may reduce the efficacy of furosemide and thiazide diuretics, due to prostaglandin synthesis inhibition at renal level. This feature must be considered in case of combined therapy.
Owing to a possible strengthening effect of oral anticoagulants, prothrombin time must be monitored during the 1st treatment week and a possible adjustment of the anticoagulant dose is to be scheduled in case of concomitant prolonged treatment.
A reduction of the hypotensive effect of β-blocking drugs, as well as a strengthening of the possible ulcerogenic effect after concomitant administration of corticosteroids can also be observed thus, requiring due caution in case of combined therapy. In some isolated cases, an increase in plasma levels of digoxin, phenytoin and lithium after concomitant administration of ibuprofen was reported.
Ibuprofen administration may occasionally increase methotrexate toxicity thus, requiring due caution in case of combined therapy. Ibuprofen must not be used in association with other NSAIDs eg, acetylsalicylic acid and paracetamol.
After concomitant administration of H₂-antagonists, no significant effect on their plasma levels was observed.

Store at room temperature (25±2°C).
Shelf-Life: 3 years.

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)

M01AE01 - ibuprofen ; Belongs to the class of propionic acid derivatives of non-steroidal antiinflammatory and antirheumatic products.

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