Ibuprofen: Package Insert and Label Information (Page 2 of 3)

Drug Interactions

ACE-inhibitors:
Reports suggest that NSAIDs may diminish the antihypertensive effect of ACE-inhibitors. This interaction should be given consideration in patients taking NSAIDs concomitantly with ACE-inhibitors.

Aspirin
When ibuprofen tablets are administered with aspirin, its protein binding is reduced, although the clearance of free ibuprofen tablets is not altered. The clinical significance of this interaction is not known; however, as with other NSAIDs, concomitant administration of ibuprofen and aspirin is not generally recommended because of the potential for increased adverse effects.

Diuretics
Clinical studies, as well as post marketing observations, have shown that ibuprofen tablets can reduce the natriuretic effect of furosemide and thiazides in some patients. This response has been attributed to inhibition of renal prostaglandin synthesis. During concomitant therapy with NSAIDs, the patient should be observed closely for signs of renal failure [see WARNINGS, Renal Effects], as well as to assure diuretic efficacy.

Lithium
Ibuprofen produced an elevation of plasma lithium levels and a reduction in renal lithium clearance in a study of eleven normal volunteers. The mean minimum lithium concentration increased 15% and the renal clearance of lithium was decreased by 19% during this period of concomitant drug administration.

This effect has been attributed to inhibition of renal prostaglandin synthesis by ibuprofen. Thus, when ibuprofen and lithium are administered concurrently, subjects should be observed carefully for signs of lithium toxicity. (Read circulars for lithium preparation before use of such concurrent therapy.)

Methotrexate
NSAIDs have been reported to competitively inhibit methotrexate accumulation in rabbit kidney slices. This may indicate that they could enhance the toxicity of methotrexate. Caution should be used when NSAIDs are administered concomitantly with methotrexate.

Warfarin-type anticoagulants
Several short-term controlled studies failed to show that ibuprofen tablets significantly affected prothrombin times or a variety of other clotting factors when administered to individuals on coumarin-type anticoagulants. However, because bleeding has been reported when ibuprofen tablets and other NSAIDs have been administered to patients on coumarin-type anticoagulants, the physician should be cautious when administering ibuprofen tablets to patients on anticoagulants. The effects of warfarin and NSAIDs on GI bleeding are synergistic, such that the users of both drugs together have a risk of serious GI bleeding higher than users of either drug alone.

H-2 Antagonists
In studies with human volunteers, co-administration of cimetidine or ranitidine with ibuprofen had no substantive effect on ibuprofen serum concentrations.

Pregnancy

Teratogenic effects: Pregnancy Category C
Reproductive studies conducted in rats and rabbits have not demonstrated evidence of developmental abnormalities. However, animal reproduction studies are not always predictive of human response. There are no adequate and well-controlled studies in pregnant women. Ibuprofen should be used in pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nonteratogenic effects
Because of the known effects of NSAIDs on the fetal cardiovascular system (closure of ductus arteriosus), use during late pregnancy should be avoided.

Labor and Delivery In rat studies with NSAIDs, as with other drugs known to inhibit prostaglandin synthesis, an increased incidence of dystocia, delayed parturition, and decreased pup survival occurred. The effects of ibuprofen tablets on labor and delivery in pregnant women are unknown.

Nursing Mothers

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from ibuprofen tablets, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use

Safety and effectiveness of ibuprofen tablets in pediatric patients have not been established.

Geriatric Use

As with any NSAIDs, caution should be exercised in treating the elderly (65 years and older).

ADVERSE REACTIONS

The most frequent type of adverse reaction occurring with ibuprofen tablets is gastrointestinal. In controlled clinical trials the percentage of patients reporting one or more gastrointestinal complaints ranged from 4% to 16%.

In controlled studies when ibuprofen tablets were compared to aspirin and indomethacin in equally effective doses, the overall incidence of gastrointestinal complaints was about half that seen in either the aspirin- or indomethacin-treated patients.

Adverse reactions observed during controlled clinical trials at an incidence greater than 1% are listed in the table. Those reactions listed in Column one encompass observations in approximately 3,000 patients. More than 500 of these patients were treated for periods of at least 54 weeks.

Still other reactions occurring less frequently than 1 in 100 were reported in controlled clinical trials and from marketing experience. These reactions have been divided into two categories: Column two of the table lists reactions with therapy with ibuprofen tablets where the probability of a causal relationship exists: for the reactions in Column three, a causal relationship with ibuprofen tablets has not been established.

Reported side effects were higher at doses of 3200 mg/day than at doses of 2400 mg or less per day in clinical trials of patients with rheumatoid arthritis. The increases in incidence were slight and still within the ranges reported in the table.

*
Reactions are classified under “Probable Causal Relationship (PCR)” if there has been one positive rechallenge or if three or more cases occur which might be causally related. Reactions are classified under “Causal Relationship Unknown” if seven or more events have been reported but the criteria for PCR have not been met.
Reactions occurring in 3% to 9% of patients treated with ibuprofen tablets. (Those reactions occurring in less than 3% of the patients are unmarked.)

Incidence Greater Than 1% (but less than 3%) Probable Causal Relationship

Precise Incidence Unknown (but less than 1%) Probable Causal Relationship *

Precise Incidence Unknown (but less than 1%) Causal Relationship Unknown**

GASTROINTESTINAL

Nausea , epigastric pain , heartburn , diarrhea, abdominal distress, nausea and vomiting, indigestion, constipation, abdominal cramps or pain, fullness of Gl tract (bloating and flatulence)

Gastric or duodenal ulcer with bleeding and/or perforation, gastrointestinal hemorrhage, melena, gastritis, hepatitis, jaundice, abnormal liver function tests; pancreatitis

CENTRAL NERVOUS SYSTEM

Dizziness , headache, nervousness

Depression, insomnia, confusion, emotional liability, somnolence, aseptic meningitis with fever and coma [see PRECAUTIONS]

Paresthesias, hallucinations, dream abnormalities, pseudotumor cerebri

DERMATOLOGIC

Rash (including maculopapular type), pruritus

Vesiculobullous eruptions, urticaria, erythema multiforme, Stevens-Johnson syndrome, alopecia

Toxic epidermal necrolysis, photoallergic skin reactions

SPECIAL SENSES

Tinnitus

Hearing loss, amblyopia (blurred and/or diminished vision, scotomata and/or changes in color vision) [see PRECAUTIONS]

Conjunctivitis, diplopia, optic neuritis, cataracts

HEMATOLOGIC

Neutropenia, agranulocytosis, aplastic anemia, hemolytic anemia (sometimes Coombs positive), thrombocytopenia with or without purpura, eosinophilia, decreases in hemoglobin and hematocrit [see PRECAUTIONS]

Bleeding episodes (e.g., epistaxis, menorrhagia)

METABOLIC/ENDOCRINE

Decreased appetite

Gynecomastia, hypoglycemic reaction, acidosis

CARDIOVASCULAR

Edema, fluid retention (generally responds promptly to drug discontinuation) [see PRECAUTIONS]

Congestive heart failure in patients with marginal cardiac function, elevated blood pressure, palpitations

Arrhythmias (sinus tachycardia, sinus bradycardia)

ALLERGIC

Syndrome of abdominal pain, fever, chills, nausea and vomiting; anaphylaxis; bronchospasm [see CONTRAINDICATIONS]

Serum sickness, lupus erythematosus syndrome, Henoch-Schonlein vasculitis, angioedema

RENAL

Acute renal failure [see PRECAUTIONS], decreased creatinine clearance, polyuria, azotemia, cystitis, hematuria

Renal papillary necrosis

MISCELLANEOUS

Dry eyes and mouth, gingival ulcer, rhinitis tests

To report SUSPECTED ADVERSE REACTIONS, contact Amneal Pharmaceuticals at 1-877-835-5472 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch

OVERDOSAGE

Approximately 1½ hours after the reported ingestion of from 7 to 10 ibuprofen tablets (400 mg), a 19-month old child weighing 12 kg was seen in the hospital emergency room, apneic and cyanotic, responding only to painful stimuli. This type of stimulus, however, was sufficient to induce respiration. Oxygen and parenteral fluids were given; a greenish-yellow fluid was aspirated from the stomach with no evidence to indicate the presence of ibuprofen. Two hours after ingestion the child’s condition seemed stable; she still responded only to painful stimuli and continued to have periods of apnea lasting from 5 to 10 seconds. She was admitted to intensive care and sodium bicarbonate was administered as well as infusions of dextrose and normal saline. By four hours post-ingestion she could be aroused easily, sit by herself and respond to spoken commands. Blood level of ibuprofen was 102.9 mcg/mL approximately 8½ hours after accidental ingestion. At 12 hours she appeared to be completely recovered. In two other reported cases where children (each weighing approximately 10 kg) accidentally, acutely ingested approximately 120 mg/kg, there were no signs of acute intoxication or late sequelae. Blood level in one child 90 minutes after ingestion was 700 mcg/mL — about 10 times the peak levels seen in absorption-excretion studies.

A 19-year old male who had taken 8,000 mg of ibuprofen over a period of a few hours complained of dizziness, and nystagmus was noted. After hospitalization, parenteral hydration and three days bed rest, he recovered with no reported sequelae.

In cases of acute overdosage, the stomach should be emptied by vomiting or lavage, though little drug will likely be recovered if more than an hour has elapsed since ingestion. Because the drug is acidic and is excreted in the urine, it is theoretically beneficial to administer alkali and induce diuresis. In addition to supportive measures, the use of oral activated charcoal may help to reduce the absorption and reabsorption of ibuprofen tablets.

DOSAGE AND ADMINISTRATION

Carefully consider the potential benefits and risks of ibuprofen tablets and other treatment options before deciding to use ibuprofen tablets. Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals [see WARNINGS].

After observing the response to initial therapy with ibuprofen tablets, the dose and frequency should be adjusted to suit an individual patient’s needs.

Do not exceed 3200 mg total daily dose. If gastrointestinal complaints occur, administer ibuprofen tablets with meals or milk.

Rheumatoid arthritis and osteoarthritis, including flare-ups of chronic disease:
Suggested Dosage: 1200 mg to 3200 mg daily (400 mg, 600 mg or 800 mg tid or qid). Individual patients may show a better response to 3200 mg daily, as compared with 2400 mg, although in well-controlled clinical trials patients on 3200 mg did not show a better mean response in terms of efficacy.

Therefore, when treating patients with 3200 mg/day, the physician should observe sufficient increased clinical benefits to offset potential increased risk.

The dose should be tailored to each patient, and may be lowered or raised depending on the severity of symptoms either at time of initiating drug therapy or as the patient responds or fails to respond.

In general, patients with rheumatoid arthritis seem to require higher doses of ibuprofen tablets than do patients with osteoarthritis.

The smallest dose of ibuprofen tablets that yields acceptable control should be employed. A linear blood level dose-response relationship exists with single doses up to 800 mg [See CLINICAL PHARMACOLOGY for effects of food on rate of absorption].

The availability of four tablet strengths facilitates dosage adjustment.

In chronic conditions, a therapeutic response to therapy with ibuprofen tablets is sometimes seen in a few days to a week but most often is observed by two weeks. After a satisfactory response has been achieved, the patient’s dose should be reviewed and adjusted as required.

Mild to moderate pain: 400 mg every 4 to 6 hours as necessary for relief of pain.

In controlled analgesic clinical trials, doses of ibuprofen tablets greater than 400 mg were no more effective than the 400 mg dose.

Dysmenorrhea: For the treatment of dysmenorrhea, beginning with the earliest onset of such pain, ibuprofen tablets should be given in a dose of 400 mg every 4 hours as necessary for the relief of pain.

HOW SUPPLIED

Ibuprofen Tablets, USP are available in the following strengths, colors and sizes:

400 mg white, round, biconvex, aqueous film-coated tablets, debossed “IP 464″ on obverse and plain on reverse. They are available as follows:
Unit dose packages of 100 (10 x 10) NDC 60687-446-01

600 mg white, oval-shaped, biconvex, aqueous film-coated tablets, debossed “IP 465″ on obverse and plain on reverse. They are available as follows:
Unit dose packages of 100 (10 x 10) NDC 60687-457-01

800 mg white, capsule-shaped, biconvex, aqueous film-coated tablets, debossed “IP 466″ on obverse and plain on reverse. They are available as follows:
Unit dose packages of 100 (10 x 10) NDC 60687-468-01

Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature]. Avoid excessive heat 40°C (104°F).

FOR YOUR PROTECTION: Do not use if blister is torn or broken.

DrugInserts.com provides trustworthy package insert and label information about marketed drugs as submitted by manufacturers to the US Food and Drug Administration. Package information is not reviewed or updated separately by DrugInserts.com. Every individual package label entry contains a unique identifier which can be used to secure further details directly from the US National Institutes of Health and/or the FDA.

As the leading independent provider of trustworthy medication information, we source our database directly from the FDA's central repository of drug labels and package inserts under the Structured Product Labeling standard. Our material is not intended as a substitute for direct consultation with a qualified health professional.

Terms of Use | Copyright © 2020. All Rights Reserved.