ALIVIO- ibuprofen tablet

Alivio by

Drug Labeling and Warnings

Alivio by is a Prescription medication manufactured, distributed, or labeled by Alivio Medical Products, LLC. Drug facts, warnings, and ingredients follow.

Drug Details [pdf]

BOXED WARNING

(What is this?)

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 (See WARNINGS).
• Ibuprofen tablets are contraindicated for treatment of peri-operative pain in the setting of coronary artery bypass graft (CABG) surgery (see WARNINGS).

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 wihtout warning symptoms. Elderly patients are at greater risk for serious gastrointestinal events (see WARNINGS).
  

DESCRIPTION

Each tablet contains: Ibuprofen, USP ......600 mg

DOSAGE & ADMINISTRATION

DOSAGE AND USE: See package insert for complete product information

DESCRIPTION

Ibuprofen tablets contain the active ingredient ibuprofen, which is (+/-) - 2 - (p - isobutylphenyl)

propionic acid. Ibuprofen is a white powder with a melting point of 74 - 77 C and is very slightly soluble

in water  (less than 1 mg / mL) and readily soluble in organic solvents such as ethanol and acetone.

Ibuprofen tablets, a nonsteroidal anti - inflammatory drug (NSAID), are available in 400 mg, 600 mg and

800 mg tablets for oral administration. Inactive ingredients: colloidal silicon dioxide, croscarmellose

sodium, magnesium stearate, microcrystalline cellulose, polyethylene glycol, polyvinyl alcohol,

pregelatinized starch, talc and titanium dioxide.

CLINICAL PHARMACOLOGY

Ibuprofen tablets contain ibuprofen which possesses analgesic and antipyretic activities. Its mode of

action, like that of other NSAIDs, is not completely understood, but may be related to prostaglandin

synthetase inhibition.

In clinical studies in patients with rheumatoid arthritis and osteoarthritis, ibuprofen tablets have benn

shown to be comparable to aspirin in controlling pain and inflammation and to be associated with a

statistically significant reduction in the milder gastrointestinal side effects ( see ADVERSE REACTIONS).

Ibuprofen tablets may be well tolerated in some patients who have had gastrointestinal side effects

with aspirin, but these patients when treated with ibuprofen tablets should be carefully followed for

signs and symptoms of gastrointestinal ulceration and bleeding. Although it is not definitely known

whether ibuprofen tablets causes less peptic ulceration than aspirin, in one study involving 885

patients with rheumatoid arthritis treated for up to one year, there were no reports of gastric ulceration

with ibuprofen tablets whereas frank ulceration was reported in 13 patients in the aspirin group

(statistically significant p less than .001).

Gastropic studies at varying doses show an increased tendency toward gastric irritation at higher

doses. However, at comparable doses, gastric irritation is approximately half that seen with aspirin.

Studies using 51 Cr - taggedred cells indicate that fecal blood loss associated with ibuprofen tablets in

doses up to 2400 mg daily did not exceed the normal range, and was significantly less than that seen

in aspirin - treated patients.

In clinical studies in patients with rheumatoid arthritis, ibuprofen tablets have been shown to be

comparable to indomethacin in controlling the signs and symptoms of disease activity and to be

associated with a statistically signifcant reduction of the milder gastrointestinal (see ADVERSE

REACTIONS ) and CNS side effects.

Ibuprofen tablets may be used in combination with gold salts and / or corticosteroids.

Controlled studies have demonstrated that ibuprofen tablets are a more effective analgesic than

propoxyphene for the relief of episiotomy pain, pain following dental extraction procedures, and for

the relief of the symptoms of primary dysmenorrhea.

In patients with primary dysmenorrhea, ibuprofen tablets have been shown to reduce elevated levels

of prostaglandin activity in the menstrual fluid and to reduce resting and active intrauterine pressure,

as well as the frequency of uterine contractions. The probable mechanism of action is to inhibit

prostaglandin synthesis rather than simply to provide analgesia.

The ibuprofen in ibuprofen tablets is rapidly absorbed. Peak serum levels are generally

attained one to two hours after administration. With single doses up to 800 mg, a linear relationship

exists between amount of drug administered and the integrated area under the serum drug

concentration vs time curve. Above 800 mg, however, the area under the curve increases less than

proprotional to increases in dose. There is no evidence of drug accumulation or enzyme induction.

The adminstration of ibuprofen tablets either under fasting conditions or immediately before meals

yields quite similar serum ibuprofen concentration - time profiles. When ibuprofen tablets are

administered immediately after a meal, there is a reduction in the rate of absorption but no appreciable

decrease in the extent of absorption. The bioavailablity of the drug is minimally altered by

the presence of food.

A bioavailablity study has shown that there was no interference with the absorption of ibuprofen

when ibuprofen tablets were given in conjunction with an antacid containing both aluminum

hydroxide and magnesium hydroxide.

Ibuprofen is readily metabolized and eliminated in the urine. The excretion of ibuprofen is virtually

complete 24 hours after the last dose. The serum half - life is 1.8 to 2.0 hours.

Studies have shown that following ingestion of the drug, 45 % to 79 % of the dose was recovered in the

urine within 24 hours as metabolite A (25 %), (+) - 2 - [p - (2hydroxymethyl - propyl) phenyl] propionic acid

and metabolite B (37 %), (+) - [p - (2carboxypropyl) phenyl] propionic acid; the percentages of free acid and

conjugated ibuprofen were approximately 1 % and 14 %, respectively.

INDICATIONS & USAGE

INDICATIONS AND USAGE

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).

Ibuprofen tablets are indicated for relief of the signs and symptoms of rheumatoid arthritis and

osteoarthritis.

Ibuprofen tablets are indicated for the relief of mild to moderate pain.

Ibuprofen tablets are also indicated for the treatment of primary dysmenorrhea.

Controlled clinical trials to establish the safety and effectiveness of ibuprofen tablets in children have

not been conducted.

CONTRAINDICATIONS

CONTRAINDICATIONS

Ibuprofen tablets are contraindicated in patients with known hypersensitivity to ibuprofen.

Ibuprofen tablets should not be given to patients who have experienced asthma, urticaria, or allergic -

type reactions after taking aspirin or other NSAIDs. Severe, rarely fatal, anaphylactic-like reactions to

NSAIDs have been reported in such patients (see WARNINGS, ANAPHYLACTOID REACTIONS, and

PRECAUTIONS, PREEXISTING ASTHMA).

Ibuprofen tablets are contraindicated for the treatment of peri-operative pain in the setting of coronary artery

bypass graft (CABG) surgery (see WARNINGS).

WARNINGS

WARNINGS

Cardiovascular Effects

Cardiovascular Thrombotic Events

Clinical trials of several COX - 2 selective and nonselective NSAIDs of up to three years duration have

shown an increased risk of serious cardiovascular (CV) thrombotic events, myocardial infarction, and stroke,

which can be fatal. All NSAIDs, both COX - 2 selective and nonselective, may have a similar risk.

Patients with a known CV disease or risk factors for CV disease may be at greater risk. To minimize the

potential risk for an adverse CV event in patients treated with an NSAID, the lowest effective dose should be used for the shortest

duration possible. Physicians and patients should remain alert for the

development of such events, even in the absence of previous CV symptoms. Patients should be

informed about the signs and/or symptoms of serious CV events and the steps to take if they occur.

There is not consistent evidence that concurrent use of aspirin mitigates the increased risk of serious

CV thrombotic events associated with NSAID use. The concurrent use of aspirin and an NSAID does

increase the risk of serious GI events (see WARNINGS, GASTROINTESTINAL EFFECTS -RISK OF

ULCERATION, BLEEDING AND PERFORATION).

Two large, controlled clinical trials of a COX-2 selective NSAID for the treatment of pain in the first

10  - 14 days following CABG surgery found an increased incidence of myocardial infarction and stroke (see

CONTRAINDICATIONS).

Hypertension

NSAIDs including ibuprofen tablets, can lead to onset of new hypertension or worsening of

pre-existing hypertension, either of which may contribute to the increased incidence of CV events. Patients

taking thiazides or loop diuretics may have impaired response to these therapies when taking NSAIDs.

NSAIDs, including ibuprofen tablets, should be used with caution in patients with hypertension. Blood

pressure (BP) should be monitored closely during the initiation of NSAID treatment and throughout the course

of therapy.

Congestive Heart Failure and Edema.

Fluid retention and edema have been observed in some patients taking NSAIDs. Ibuprofen tablets

should be used with caution in patients with fluid rentention or heart failure.

Gastrointestinal Effects - Risk of Ulceration, Bleeding and Perforation

NSAIDs, including ibuprofen tablets, can cause serious gastrointestinal (GI) adverse events including inflammation, bleeding, ulceration, and perforation of

the stomach, small intestine, or large intestine, which can be fatal. These serious adverse events can occur at any time, with or without warning symptoms, in

patients treated with NSAIDs. Only one in five patients, who develop a serious upper GI adverse event on NSAID therapy, is symptomatic. Upper GI ulcers,

gross bleeding, or perforation caused by NSAIDs occur in approximately 1 % of patients treated for 3 - 6 months, and in about 2 - 4 % of patients treated for one

year. These trends continue with longer duration of use, increasing the likelihood of developing a serious GI event at some time during the course of

therapy. However, even short - term therapy is not without risk. NSAIDs should be prescribed with extreme caution in those with a prior history of ulcer

disease or gastrointestinal bleeding. Patients with a prior history of peptic ulcer disease and / or gastrointestinal bleeding who use NSAIDs have a greater

than 10 - fold increased risk for developing a GI bleed compared to patients treated with neither of these risk factors. Other factors that increase the risk of

GI bleeding in patients treated with NSAIDs include concomitant use of oral corticosteroids or anticoagulants, longer duration of NSAID therapy,

smoking, use of alcohol, older age, and poor general health status. Most spontaneous reports of fatal GI events are in elderly or debilitated

patients and therefore, special care should be taken in treating this population.

To minimize the potential risk for an adverse GI event in patients treated with an NSAID, the lowest effective dose should be used for the shortest

possible duration. Patients and physicians should remain alert for signs and symptoms of GI ulcerations and bleeding during NSAID therapy and

promptly initiate additional evaluation and treatment is a serious GI event is suspected. This should include discontinuation of the NSAID until a

serious GI adverse event is ruled out. For high - risk patients, alternate therapies that do not involve NSAIDs should be considered.

Renal Effects

Long - term administration of NSAIDs has resulted in renal papillary necrosis and other renal injury. Renal toxicity has also been seen in patients

in whom renal prostaglandins have a compensatory role in the maintenance of renal perfusion. In these patients, administration of a NSAID

may cause a dose - dependent reduction in prostaglandin formation and, secondarily, in renal blood flow, which may precipitate overt renal decomposition.

Patients at greatest risk of this reaction are those with impaired renal function, heart failure, liver dysfunction, those taking diuretics and ACE inhibitors,

and the elderly. Discontinuation of NSAID therapy is usually followed by recovery to the pretreatment state.

Advanced Renal Disease

No information is available from controlled clinical studies regarding the use of ibuprofen tablets in patients with advanced renal disease. Therefore,

treatment with ibuprofen tablets is not recommended in those patients with advanced renal disease. If ibuprofen tablet therapy must be initiated,

close monitoring of the patients renal function is advisable.

Anaphylactoid Reactions

As with other NSAIDs, anaphylactoid reactions may occur in patients without known prior exposure to ibuprofen tablets. Ibuprofen tablets should not

be given to patients with the aspirin triad. This symptom complex typically occurs in asthmatic patients who experience rhinitis with or without nasal

polyps, or who exhibit severe, potentially fatal bronchospasm after taking aspirin or other NSAIDs (see CONTRAINDICATIONS and PRECAUTIONS,

Preexisting Asthma). Emergency help should be sought in cases where an anaphylactoid reaction occurs.

Skin Reactions

NSAIDs, including ibuprofen tablets, can cause serious skin adverse events such as exfoliative dermatitis. Stevens - Johnson Syndrome (SJS), and

toxic epidermal necrolysis (TEN), which can be fatal. These serious events may occur without warning. Patients should be informed about the signs

and symptoms of serious skin manifestations and use of the drug should be discontinued at the first appearance of skin rash or any other

sign of hypersensitivity.

Pregnancy

In late pregnancy, as with other NSAIDs, ibuprofen tablets should be avoided because it may cause premature closure of the ductus arteriosus.

PRECAUTIONS

PRECAUTIONS

General

Ibuprofen tablets cannot be expected to substitute for corticosteroids or to treat corticosteroid insufficiency. Abrupt discontinuation of corticosteroids may

led to disease exacerbation. Patients with prolonged corticosteroids therapy should have their therapy tapered slowly if a decision is made to discontinue

corticosteroids.

The pharmacological activity of ibuprofen tablets in reducing fever and inflammation may diminish the utility of these diagnostic signs in detecting

complications of presumed noninfections, painful conditions.

Hepatic effects

Borderline elevations of one or more liver tests may occur in up to 15 % of patients taking NSAIDs, including ibuprofen tablets. These laboratory

abnormalities may progress, may remain unchanged, or may ne transient with continuing therapy. Notable elevations of ALT or AST (approximately

three or more times the upper limit of normal) have been reported in approximately 1 % of patients in clinical trials with NSAIDs. In addition, rare cases

of severe hepatic reactions, including jaundice, fulminant hepatitis, liver necrosis, and hepatic failure, some of them with fatal outcomes have been reported.

A patient with symptoms and/or signs suggesting liver dysfunction, or with abnormal liver test values, should be evaluated for evidence of the development

of a more severe hepatic reaction while on therapy with ibuprofen tablets. If clinical signs and symptoms consistent with liver disease develop, or is systemic

manifestations occur (e.g. eosinophilia, rash, etc.), ibuprofen tablets should be discontinued.

Hematological effects

Anemia is sometimes seen in patients receiving NSAIDs, including ibuprofen tablets. This may be due to fluid retention, occult or gross GI blood loss, or an

incompletely described effect upon erythropoiesis. Patients on long - term treatment with NSAIDs, including ibuprofen tablets, should have their hemoglobin

or hematocrit checked if they exhibit any signs or symptoms of anemia.

In two postmarketing clinical studies the incidence of a decreased hemoglobin level was greater than previously reported. Decrease in hemoglobin of 1 gram

or more was observed in 17.1 % of 193 patients on 1600 mg ibuprofen daily (osteoarthritis) and in 22.8 % of 189 patients taking 2400 mg of ibuprofen daily

(rheumatoid arthritis). Positive stool occult blood tests and elevated serum creatinine levels were also observed in these studies.

NSAIDs inhibit platelet aggregation  and have been shown to prolong bleeding time in some patients. Unlike aspirin, their effect on platelet function is

quantitatively less, of shorter duration, and reversible.

Patients receiving ibuprofen tablets who may be adversely affected by alterations in platelet function, such as those with coagulation disorders or patients

receiving anticoagulants should be carefully monitored.

Preexisting asthma

Patients with asthma may have aspirin - sensitive asthma. The use of aspirin in patients with aspirin - sensitive asthma has been associated with severe

bronchospasm, which can be fatal. Since cross reactivity, including bronchospasm, between aspirin and NSAIDs has been reported in such aspirin - sensitive

patients, ibuprofen tablets should not be administered to patients with this form of aspirin sensitivity and should be used in conjunction in patients with

preexisting asthma.

Ophthalmological effects

Blurred and/or diminished vision, scotomata, and/or changes in color vision have been reported. If a patient develops such complaints while receiving

ibuprofen tablets, the drug should be discontinued, and the patient should have an ophthalmological examination which includes central visual fields and color

vision testing.

Aseptic Meningitis

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 tablets, the possibility of its being related to ibuprofen tablets should be

considered.

Information for Patients

Patients should be informed of the following information before initiating therapy with an NSAID and periodically during the course of ongoing

therapy. Patients should also be encouraged to read the NSAID Medication Guide that accompanies each prescription dispensed.

-Ibuprofen tablets like other NSAIDs, may cause serious CV side effects, such as MI or stroke, whichmay result in hospitalization and even death.

Although serious CV events can occur without warning symptoms, patients should be alert for the signs and symptoms of chest paid, shortness of breath,

weakness, slurring of speech, and should ask for medical advice when observing any indicative sign or symptoms. Patients should be apprised of the

importance of this follow - up (see WARNINGS, Cardiovascular Effects).

-Ibuprofen tablets, like other NSAIDs, can cause GI discomfort and, rarely, serious GI side effects, such as ulcers and bleeding, which may result in

hospitalization and even death. Although serious GI tract ulcerations and bleeding can occur without warning symptoms, patients should be alert for the

signs and symptoms of ulcerations and bleeding, and should ask for medical advice when observing any indicative signs or symptoms including

epigastric pain, dyspepsia, melena, and hematemesis. Patients should be apprised of the importance of this follow - up (see WARNINGS,

Gastrointestinal Effects - Risk of Ulceration, Bleeding and Perforation).

-Ibuprofen tablets, like other NSAIDs, can cause serious skin side effects such as exfoliative dermatitis, SJS and TEN, which may result in hospitalization

and even death. Although serious skin reactions may occur without warning, patients should be alert for the signs amd symptoms of skin rash and

blisters, fever, or other signs hypersensitivity such as itching, and should ask for medical advice when observing any indicative sign or symptoms.

Patients should be advised to stop the drug immediately if they develop any type of rash and contact their physicians as soon as possible.

-Patients should promptly report signs or symptoms of unexplained weight gain or edema to their physicians.

-Patients should be informed of the warning signs and symptoms of hepatoxicity (e.g. nauseam fatigue,lethargy, pruritus, jaundice, right upper quadrant

tenderness and flu-like symptoms). If these occur, patients should be instructed to stop therapy and seek immediate medical therapy.

-Patients should be informed of the signs of anaphylactoid reaction (e.g. difficulty breathing, swelling of the face or throat). If these occur, patients

should be instructed to seek immediate emergency help (see WARNINGS).

-In late pregnancy, as with other NSAIDs, ibuprofen tablets should be avoided because it may cause premature closure of the ductus arteriosus.

Laboratory Tests

Because serious GI tract ulcerations and bleeding can occur without warning symptoms, physicians should monitor for signs or symptoms of GI bleeding.

Patients on long - term treatment with NSAIDs should have their CBC and chemistry profile checked periodically. If clinical signs and symptoms consistent

with liver or renal disease develop, systemic manifestations occur (e.g. eosinophilia, rash, etc), or abnormal liver tests persists or worsen, ibuprofen tablets

should be discontinued.

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 reporduction studies

are not always predictive of human response. There are no adequate and well - controlled studies in pregnant women. Ibuprofen tablets 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

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 were ranged form 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. These 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 form 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 were slight and still within the ranges reported in the table.

OVERDOSAGE

OVERDOSAGE

Approximately 1 1/2 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 ro 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 ug / mL approxiamtely

8 1/2 hours after accidental ingestion. As 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 ug / 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, through 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 & ADMINISTRATION

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 - 3200 mg daily (300 mg qid; 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 the 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 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

HOW SUPPLIED

Ibuprofen tablets are available in the following strengths:

400 mg (White to off white, round, biconvex, film coated tablets debossed with '121' on one side and

plain on the other side)

Bottles of 90     (NDC: 69512-400-90)

600 mg (White to off white, capsule shaped, biconvex, film coated tablets debossed with '122' on one side and plain

on other side)

Bottles of 90     (NDC: 69512-600-90)

800 mg (White to off white, capsule shaped, biconvex, film coated tablets debossed with '123' on

one side and plain on other side)

Bottles of 90     (NDC: 69512-800-90)

Store at 20 to 25 C (68 to 77 F) [See USP Controlled Room Temperature]

Rx only

Distributed by:

Able Wholesalers

1329A Baptist World Center Dr.

Nashville, TN 37207

MEDICATION GUIDE

Medication Guide for Non-Steroidal

Anti-Inflammatory Drugs (NSAIDs)

(See the end of this Medication Guide for a list of

prescription NSAID medicines)

What is the most important information I should know

about medicines called Non-Steroidal Anti-Inflammatory

Drugs (NSAIDs)?

NSAID medicines may increase the chance of a heart attack

or stroke that can lead to death.This chance increases:

-with longer use of NSAID medicines

-in people who have heart disease

NSAID medicines should never be used right before or after

a heart surgery called a "coronary artery bypass

graft (CABG)."

NSAID medicines can cause ulcers and bleeding in the

stomach and intestines at any time during treatment.

Ulcers and bleeding:

-can happen without warning symptoms

-may cause death.

The chance of a person getting an ulcer or bleeding

increases with:

-taking medicines called "corticosteroids" and "anticoagulants"

-longer use

-smoking

-drinking alcohol

-older age

-having poor health

NSAID medicines should only be used:

-exactly as prescribed

-at the lowest dose possible for your treatment

-for the shortest time needed

What are Non-Steroidal Anti-Inflammatory Drugs

(NSAIDs)?

NSAID medicines are used to treat pain and redness, swelling,

and heat (inflammation) form medical conditions such as:

-different types of arthritis

-menstrual cramps and other types of short-term pain

Who should not take a Non-Steroidal Anti-Inflammatory

Drug (NSAID)?

Do not take an NSAID medicine:

-if you had an asthma attack, hives, or other allergic

reaction with aspirin or any other NSAID medicine

-for pain right before or after heart bypass surgery

Tell your healthcare provider:

-about all of your medical conditions

-about all of the medicines you take. NSAIDs and some

other medicines can interact with each other and cause

serious side effects. Keep a list of your medicines to

show to your healthcare provider and pharmacist.

-if you are pregnant. NSAID medicines should not be

used by pregnant women late in their pregnancy.

-if you are breastfeeding. Talk to your doctor.

What are the possible side effects of Non-Steroidal Anti-

Inflammatory Drugs (NSAIDs)?

Serious side effects include:                    Other side effects include:

-heart attack                                                -stomach pain

-stroke                                                         -constipation

-high blood pressure                                     -diarrhea

-heart failure from body

swelling (fluid retention)                                -gas

-kidney problems including

kidney failure                                               -heartburn

-bleeding and ulcers in the stomach

and intestines                                              -nausea

-low red blood cells

(anemia)                                                     -vomiting

-life-threatening skin

reactions                                                    -dizziness

-life-threatening allergic reactions

-liver problems including liver failure

-asthma attacks in people who have asthma

Get emergency help right away if you have any of the

following symptoms:

-shortness of breath or trouble breathing

-chest pain

-weakness in one part or side of your body

-slurred speech

-swelling of the face or throat

Stop your NSAID medicine and call your healthcare provider

right away if you have any of the following symptoms:

-nausea

-more tired or weaker than usual

-itching

-your skin or eyes look yellow

-stomach pain

-flu-like symptoms

-vomit blood

-there is blood in your bowel movement or it is black and

sticky like tar

-unusual weight gain

-skin rash or blisters with fever

-swelling of the arms and legs, hands and feet

These are not all the side effects with NSAID medicines. Talk

to your healthcare provider or pharmacist for more information

about NSAID medicines.

Other information about Non-Steroidal Anti-Inflammatory

Drugs (NSAIDs)

-Aspirin is an NSAID medicine but it does not increase the

chance of a heart attack. Aspirin can cause bleeding in the

brain, stomach and intestines. Aspirin can also cause

ulcers in the stomach and intestines.

-Some of these NSAID medicines are sold in lower doses

without a prescription (over - the - counter). Talk to your

healthcare provider before using over - the - counter NSAIDs

for more than 10 days.

NSAID medicines that need a prescription

Generic Name                                  Tradename

Celecoxib                                           Celebrex

Diclofenac                                          Cataflam, Voltaren, Arthrotec (combined with misoprostol)

Diflunisal                                            Dolobid

Etodolac                                             Lodine, Lodine XL

Fenoprofen                                         Nalfrom, Nalfrom 200

Flurbiprofen                                         Ansaid

Ibuprofen                                             Motrin, Tab-Profen, Vicoprofen (combined with hydrocodone), Combunox (combined with oxycodone)

Indomethacin                                       Indocin, Indocin SR, Indo-Lemmon, Indomethagan

Ketoprofen                                           Oruvail

Ketorolac                                              Toradol

Mefanamic Acid                                     Ponstel

Meloxicam                                             Mobic

Nabumetone                                          Relafen

Naproxen                                               Naprosyn, Anaprox, Anaprox DS, EC-Naproxyn, Neprelan, Naprapac (copackaged with lansoprazole)

Oxaprozin                                              Daypro

Piroxicam                                               Feldene

Sulindac                                                 Clinoril

Tolmetin                                                 Tolectin, Tolectin DS, Tolectin 600

-Vicoprofen contains the same dose of ibuprofen as over - the - counter

(OTC) NSAIDs, and is usually used for less than 10 days to

treat pain. The OTC NSAID label warns that long term continuous

use may increase the risk of heart attack or stroke.

These are not all the side effects with NSAID medicines. Talk

to your healthcare provider or pharmacist for more information

and NSAID medicines. Call your doctor for medical advice

about side effects. You may report side effects to FDA

at 1-800-FDA-1088 and / or Able Wholesalers at

1-800-430-9814.

This Medication Guide has been approved by the U.S. Food

and Drug Administration

Revision: R306/09

Distributed by:

Able Wholesalers

1329A Baptist World Center Dr.

Nashville, TN  37207

1-800-430-9814

PRINCIPAL DISPLAY PANEL

INGREDIENTS AND APPEARANCE

ALIVIO  
ibuprofen tablet

Product Information
Product Type	HUMAN PRESCRIPTION DRUG	Item Code (Source)	NDC: 69512-600
Route of Administration	ORAL

Active Ingredient/Active Moiety
Ingredient Name	Basis of Strength	Strength
IBUPROFEN (UNII: WK2XYI10QM) (IBUPROFEN - UNII:WK2XYI10QM)	IBUPROFEN	600 mg  in 600 mg

Inactive Ingredients
Ingredient Name	Strength
SILICON DIOXIDE (UNII: ETJ7Z6XBU4)
CROSCARMELLOSE SODIUM (UNII: M28OL1HH48)
MAGNESIUM STEARATE (UNII: 70097M6I30)
CELLULOSE, MICROCRYSTALLINE (UNII: OP1R32D61U)
POLYETHYLENE GLYCOLS (UNII: 3WJQ0SDW1A)
POLYVINYL ALCOHOL (UNII: 532B59J990)
STARCH, CORN (UNII: O8232NY3SJ)
TALC (UNII: 7SEV7J4R1U)
TITANIUM DIOXIDE (UNII: 15FIX9V2JP)

Product Characteristics
Color	white (white to off white)	Score	no score
Shape	ROUND	Size	13mm
Flavor		Imprint Code	122
Contains

Packaging
#	Item Code	Package Description	Marketing Start Date	Marketing End Date
1	NDC: 69512-600-90	90 in 1 BOTTLE
1		54000 mg in 1 BOTTLE; Type 0: Not a Combination Product

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
ANDA	ANDA090796	07/01/2015

Labeler - Alivio Medical Products, LLC (079670828)