Adverse reactions : תופעות לוואי

Adverse Reactions
Adverse Reactions Attributed to Ibuprofen
Gastrointestinal
Epigastric pain, heartburn, diarrhea, abdominal distress, nausea and vomiting, indigestion, constipation, abdominal cramps or pain, fullness of gastrointestinal tract, dyspepsia, gastrointestinal bleeding, peptic ulceration,.

Central Nervous System
Dizziness, severe headache, nervousness, convulsions, pain in the spinal column.

Dermatological
Rash (including maculopapular type), pruritus, photosensitivity, skin peeling.
Rarely exfoliative dermatitis and epidermal necrolysis have been reported with ibuprofen.

Special Senses
Hearing disturbance.

Metabolic/Endocrine
Decreased appetite.
Cardiovascular
Edema, fluid retention (generally responds to drug discontinuation, see Precautions).
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Hematological
Neutropenia,    agranulocytosis, aplastic   anemia,          hemolytic          anemia, thrombocytopenia, decreased hemoglobin and hematocrit.

Allergic
Fever.
Bronchospasm may be precipitated in patients with a history of aspirin-sensitive asthma

Other Hypersensitivity Reactions:
Rarely hypersensitivity reactions with cutaneous eruptions, urticaria and pruritus, as well as attacks of asthma, with or without drop in blood pressure, have been observed. In single cases, severe hypersensitivity reactions, manifesting as facial edema, swelling of the tongue, swelling of the larynx, dyspnea, tachycardia, hypotension or severe shock have been reported. If these symptoms occur, immediate medical attention is necessary.
In single cases, serious forms of skin reactions such as erythema multiforme can occur.
In patients with existing auto-immune disorders (systemic lupus erythematosus, mixed connective tissue disease) during treatment with ibuprofen, single cases of symptoms of aseptic meningitis such as stiff neck, headache, nausea, vomiting, fever or disorientation have been observed.
Other
Stiffness, sudden decrease in the amount of urine, black stools.
Renal papillary necrosis which can lead to renal failure.
Adverse Reactions Attributed to Codeine
Side effects to codeine include constipation, respiratory depression, cough suppression, nausea and drowsiness

Precautions
Note
Patients sensitive to one of the non-steroidal anti-inflammatory agents (NSAIDs) may be sensitive to any of the other NSAIDs also.
Blurred and/or diminished vision, scotomata, and changes in color vision have been reported. If a patient develops such complaints while receiving ibuprofen, the drug should be discontinued and the patient should have an ophthalmological examination which includes central visual fields and color vision testing.
As with other NSAIDs, patients should be cautioned about engaging in activities requiring mental alertness and motor coordination, such as driving a car.
Physicians should be consulted if patients taking ibuprofen exhibit signs or symptoms of gastrointestinal ulceration or bleeding, blurred vision or other eye symptoms, skin rash, weight gain, or edema.
Fluid retention and edema have been reported in association with ibuprofen.
Therefore, the drug should be used with caution in patients with a history of cardiac decompensation or hypertension.
Since ibuprofen is eliminated primarily by the kidneys, patients with significantly impaired renal function should be closely monitored, and a reduction in dosage should be anticipated to avoid drug accumulation.
Ibuprofen should be used with caution in individuals with intrinsic coagulation defects, and those on anticoagulant therapy.
Caution should be exercised when this product is administered to asthma sufferers since bronchospasm may be precipitated in patients suffering from, or with a previous history of bronchial asthma or allergic disease.
The elderly are at increased risk of the consequence of adverse reactions.

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Undesirable effects may be minimised by using the minimum effective dose for the shortest possible duration.
Monitoring of blood urea nitrogen (BUN), serum creatinine concentrations and/or serum potassium concentrations may be required at periodic intervals during therapy, especially in patients with documented hepatic or renal function impairment.
The same monitoring may also be required in patients known or suspected to be at risk for renal function impairment, patients taking diuretics concurrently, and in patients in whom signs of possible renal toxicity occur, such as substantial increases in blood pressure, fluid retention, or rapid weight gain.
In order to avoid exacerbation of disease or adrenal insufficiency, patients who have been on prolonged corticosteroid therapy should have their therapy reduced slowly, rather than discontinued abruptly, when ibuprofen is added to the treatment regimen.
As with other non-steroidal anti-inflammatory agents, borderline elevations of one or more liver tests may occur in up to 15% of patients. These abnormalities may progress, remain essentially unchanged, or be transient with continued therapy.
Because serious gastrointestinal tract ulcerations and bleeding can occur without warning symptoms, physicians should follow chronically treated patients for the signs and symptoms of ulcerations and bleeding and should inform them (in case of children, the child’s parent/guardian) of importance of this follow-up.
Patients with symptoms and/or signs suggesting liver dysfunction, or in whom an abnormal liver test has occurred, should be evaluated for evidence of the development of more severe hepatic reactions while on therapy with ibuprofen.
Severe hepatic reactions, including jaundice and cases of fatal hepatitis, have been reported with ibuprofen as with other non-steroidal anti-inflammatory agents.
Although such reactions are rare, if abnormal liver tests persist or worsen, or clinical signs and symptoms consistent with liver disease develop, or systemic manifestations occur (e.g., eosinophilia, rash, etc.), ibuprofen should be discontinued.
In cross-study comparisons with doses ranging from 1200-3200 mg daily for several weeks, a slight dose-response decrease in hemoglobin/hematocrit was noted.
Aseptic meningitis with fever and coma has been observed on rare occasions in patients on ibuprofen therapy. Although it is probably more likely to occur in patients with systemic lupus erythematosus and related connective tissue diseases, it has been reported in patients who do not have an underlying chronic disease. If signs or symptoms of meningitis develop in a patient on ibuprofen, the possibility of its being related to ibuprofen should be considered.

There is some evidence that drugs which inhibit cyclo-oxygenase/ prostaglandin synthesis may cause impairment of female fertility by an effect on ovulation. This is reversible on withdrawal of treatment.

Patients Who Require Surgery (Including Dental Surgery)
Caution is recommended in patients who require surgery. Most of the Nonsteroidal anti-inflammatory agents inhibit platelet aggregation and may prolong bleeding time, which may increase intra-and postoperative bleeding. Consideration should therefore be given to discontinuing NSAIDs treatment for an appropriate length of time prior to elective surgery, depending on the potency and duration of effect of the individual agent on platelet aggregability.
In case of patients requiring dental surgery, nonsteroidal anti-inflammatory agents may cause soreness, irritation, or ulceration of the oral mucosa. Most of the nonsteroidal anti-inflammatory agents may rarely cause leukopenia and/or thrombocytopenia, which may result in an increased incidence of microbial infection, delayed healing, and gingival bleeding. If leukopenia or thrombocytopenia occurs, dental work should be deferred until blood counts return to normal, and patients should be instructed in proper oral hygiene.
NUROFEN PLUS Tab   25. 12. 2005, RH                                    Page 4 of 6 Drug Interactions
Ibuprofen/Coumarin-Type Anticoagulants: Because bleeding has been reported when ibuprofen and other non-steroidal anti-inflammatory agents have been administered to patients on coumarin-type anticoagulants, physicians should exercise caution when administering ibuprofen to patients on anticoagulants.
Ibuprofen/Aspirin/Non-Steroidal Anti-Inflammatory Agents (NSAIDs): Animal studies have demonstrated that aspirin administered with NSAIDs causes a decrease in blood levels and activity of non-aspirin drugs. Since concomitant use offers no therapeutic advantage, such combinations should be avoided.
Ibuprofen/Methotrexate: Animal studies indicate that ibuprofen, as well as other NSAIDs, may enhance the toxicity of methotrexate. Caution should be used if ibuprofen is administered concomitantly with methotrexate.
Ibuprofen/Beta-Blockers: As with other nonsteroidal anti-inflammatory agents , the antihypertensive effect of beta-blockers may be reduced.
Ibuprofen/Furosemide/Thiazides: Clinical studies, as well as random observations, have shown that ibuprofen can reduce the natriuretic effect of furosemide and thiazides in some patients. During concomitant therapy with ibuprofen, patients should be observed closely for signs of renal failure, as well as to assure diuretic efficacy.
Ibuprofen/Lithium: Ibuprofen may produce an elevation of plasma lithium levels and a reduction in renal lithium clearance. Therefore, when ibuprofen and lithium are administered concurrently, subjects should be observed carefully for signs of lithium toxicity.
Ibuprofen/Alcohol: Concomitant use of non-steroidal anti-inflammatory agents with alcohol may increase the risk of gastrointestinal side effects, including ulceration or hemorrhage.
Ibuprofen/Probenecid: Probenecid may decrease excretion and increase the serum concentration of NSAIDs, possibly enhancing effectiveness and/or increasing the potential for toxicity of these agents. A decrease in dosage of the NSAIDs may be considered necessary.
Ibuprofen/Zidovudine: There is evidence of prolonged bleeding time in patients receiving concurrent treatment with zidovudine and ibuprofen.
Codeine/Monoamine Oxidase (MAO) Inhibitors: Codeine interacts with monoamine oxidase inhibitors.

Dosage and Administration
Notes
This product should be taken with or after food.
The tablets should not to be used for more than 10 days for the treatment of pain, or for more than 3 days for the treatment of fever, unless instructed by the physician.
The smallest effective dose should be used.
In primary dysmenorrhea, Nurofen Plus Tablets should be taken immediately following the onset of pain.

Recommended dosage:
Adults:
One or two tablets every four to six hours.

Children under 12 years:
Not recommended.
Elderly:
No special dosage modifications are required for elderly patients, unless renal or hepatic function is impaired, in which case dosage should be assessed individually.

Do not take more than 6 tablets in 24 hours.

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