100 mg/5 mL

Rx Only

The active ingredient in Ibuprofen Oral Suspension, USP is ibuprofen, which is a member of the propionic acid group of nonsteroidal anti-inflammatory drugs (NSAIDs). Ibuprofen is a racemic mixture of [+]S- and [-]R-enantiomers. It is a white to off-white crystalline powder, with a melting point of 74° to 77°C. It is practically insoluble in water (<0.1 mg/mL), but readily soluble in organic solvents such as ethanol and acetone. Ibuprofen has a pKa of 4.43 ± 0.03 and an n-octanol/water partition coefficient of 11.7 at pH 7.4. The chemical name for ibuprofen is (±)-2-(p-Isobutylphenyl) propionic acid. The molecular weight of ibuprofen is 206.28. Its molecular formula is C13H18O2 and it has the following structural formula:

Ibuprofen Oral Suspension, USP is a sucrose-sweetened, orange-colored, berry-flavored suspension containing 100 mg of ibuprofen in 5 mL (20 mg/mL). Inactive ingredients include: acesulfame potassium, citric acid anhydrous, D&C yellow #10, FD&C red #40, glycerin, polysorbate 80, pregelatinized corn starch, purified water, sodium benzoate, strawberry flavor, sucrose and xanthan gum.

Pharmacokinetics - Ibuprofen is a racemic mixture of [-]R-and [+]S-isomers.

In vivo and in vitro studies indicate that the [+]S-isomer is responsible for clinical activity. The [-]R-form, while thought to be pharmacologically inactive, is slowly and incompletely (~ 60%) interconverted into the active [+]S species in adults. The degree of interconversion in children is unknown, but is thought to be similar. The [-]R-isomer serves as a circulating reservoir to maintain levels of active drug. Ibuprofen is well absorbed orally, with less than 1% being excreted in the urine unchanged. It has a biphasic elimination time curve with a plasma half-life of approximately 2 hours. Studies in febrile children have established the dose-proportionality of 5 and 10 mg/kg doses of ibuprofen. Studies in adults have established the dose-proportionality of ibuprofen as a single oral dose from 50 to 600 mg for total drug and up to 1200 mg for free drug.

Absorption - In vivo studies indicate that ibuprofen is well absorbed orally from the suspension formulation, with peak plasma levels usually occurring within 1 to 2 hours (see Table 1).

Antacids - A bioavailability study in adults has shown that there was no interference with the absorption of ibuprofen when given in conjunction with an antacid containing both aluminum hydroxide and magnesium hydroxide.

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

Food Effects - Absorption is most rapid when ibuprofen is given under fasting conditions. Administration of ibuprofen with food affects the rate but not the extent of absorption. When taken with food, Tmax is delayed by approximately 30 to 60 minutes, and peak levels are reduced by approximately 30 to 50%.

Distribution - Ibuprofen, like most drugs of its class, is highly protein bound (>99% bound at 20 mcg/mL). Protein binding is saturable and at concentrations >20 mcg/mL binding is non-linear. Based on oral dosing data there is an age- or fever-related change in volume of distribution for ibuprofen. Febrile children <11 years old have a volume of approximately 0.2 L/kg while adults have a volume of approximately 0.12 L/kg. The clinical significance of these findings is unknown.

Metabolism - Following oral administration, the majority of the dose was recovered in the urine within 24 hours as the hydroxy-(25%) and carboxypropyl-(37%) phenylpropionic acid metabolites. The percentages of free and conjugated ibuprofen found in the urine were approximately 1% and 14%, respectively. The remainder of the drug was found in the stool as both metabolites and unabsorbed drug.

Elimination - Ibuprofen is rapidly metabolized and eliminated in the urine. The excretion of ibuprofen is virtually complete 24 hours after the last dose. It has a biphasic plasma elimination time curve with a half-life of approximately 2.0 hours. There is no difference in the observed terminal elimination rate or half-life between children and adults, however, there is an age- or fever-related change in total clearance. This suggests that the observed change in clearance is due to changes in the volume of distribution of ibuprofen (see Table 1 for Cl/F values).

Clinical Studies - Controlled clinical trials comparing doses of 5 and 10 mg/kg ibuprofen suspension and 10 to 15 mg/kg of acetaminophen elixir have been conducted in children 6 months to 12 years of age with fever primarily due to viral illnesses. In these studies there were no differences between treatments in fever reduction for the first hour and maximum fever reduction occurred between 2 and 4 hours. Response after 1 hour was dependent on both the level of temperature elevation as well as the treatment. In children with baseline temperatures at or below 102.5°F both ibuprofen doses and acetaminophen were equally effective in their maximum effect. In children with temperatures above 102.5°F, the ibuprofen 10 mg/kg dose was more effective. By 6 hours, children treated with ibuprofen 5 mg/kg tended to have recurrence of fever, whereas children treated with ibuprofen 10 mg/kg still had significant fever reduction at 8 hours. In control groups treated with 10 mg/kg acetaminophen, fever reduction resembled that seen in children treated with 5 mg/kg of ibuprofen, with the exception that temperature elevation tended to return 1 to 2 hours earlier.

In patients with primary dysmenorrhea, ibuprofen has been shown to reduce elevated levels of prostaglandin activity in the menstrual fluid and to reduce testing 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.

Pharmacodynamics - Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID) that possesses anti-inflammatory, analgesic and antipyretic activity. Its mode of action, like that of other NSAIDs, is not completely understood, but may be related to prostaglandin synthetase inhibition. After absorption of the racemic ibuprofen, the [-]R-enantiomer undergoes interconversion to the [+]S-form. The biological activities of ibuprofen are associated with the [+]S-enantiomer.

In a healthy volunteer study, ibuprofen 400 mg given once daily, administered 2 hours prior to immediate-release aspirin (81 mg) for 6 days, showed an interaction with the antiplatelet activity of aspirin as measured by % serum thromboxane B2 (TxB2) inhibition at 24 hours following the day-6 aspirin dose [53%]. An interaction was still observed, but minimized, when ibuprofen 400 mg given once-daily was administered as early as 8 hours prior to the immediate-release aspirin dose [90.7%]. However, there was no interaction with the antiplatelet activity of aspirin when ibuprofen 400 mg, given once daily, was administered 2 hours after (but not concomitantly, 15 min, or 30 min after) the immediate-release aspirin dose [99.2%].

In another study, where immediate-release aspirin 81 mg was administered once daily with ibuprofen 400 mg given three times daily (1, 7, and 13 hours post-aspirin dose) for 10 consecutive days, the mean % serum thromboxane B2 (TxB2) inhibition suggested no interaction with the antiplatelet activity of aspirin [98.3%]. However, there were individual subjects with serum TxB2 inhibition below 95%, with the lowest being 90.2%.

When a similarly designed study was conducted with enteric-coated aspirin, where healthy subjects were administered enteric-coated aspirin 81 mg once daily for 6 days and ibuprofen 400 mg three times daily (2, 7 and 12 h post-aspirin dose) for 6 days, there was an interaction with the antiplatelet activity at 24 hours following the day-6 aspirin dose [67%] (see PRECAUTIONS-Drug Interactions).

Carefully consider the potential benefits and risks of Ibuprofen Oral Suspension and other treatment options before deciding to use ibuprofen. Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals (see WARNINGS).

Ibuprofen is contraindicated in patients with known hypersensitivity to ibuprofen.

Ibuprofen 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 is contraindicated in the setting of coronary artery bypass graft (CABG) surgery (see WARNINGS).

In patients taking ibuprofen or other NSAIDs, the most frequently reported adverse experiences occurring in approximately 1 to 10% of patients are: Abnormal renal function, anemia, dizziness, edema, elevated liver enzymes, fluid retention, gastrointestinal experiences (including abdominal pain, bloating, constipation, diarrhea, dyspepsia, epigastric pain, flatulence, heartburn, nausea, vomiting), headaches, increased bleeding time, nervousness, pruritus, rashes (including maculopapular) and tinnitus.

Additional adverse experiences reported occasionally include:

Body as a whole - fever, infection, sepsis

Cardiovascular system - congestive heart failure in patients with marginal cardiac function, hypertension, tachycardia, syncope

Digestive system - dry mouth, duodenitits, esophagitis, gastric or duodenal ulcer with bleeding and/or perforation, gastritis, gastrointestinal bleeding, glossitis, hematemesis, hepatitis, jaundice, melena, rectal bleeding

Hemic and lymphatic system - ecchymosis, eosinophilia, leukopenia, purpura, stomatitis, thrombocytopenia

Metabolic and nutritional - weight changes

Nervous system - anxiety, asthenia, confusion, depression, dream abnormalities, drowsiness, insomnia, malaise, paresthesia, somnolence, tremors, vertigo

Respiratory system - asthma, dyspnea

Skin and appendages - alopecia, photosensitivity, sweat

Special senses - blurred vision

Urogenital system - cystitis, dysuria, hematuria, interstitial nephritis, oliguria/polyuria, proteinuria, acute renal failure in patients with pre-existing significantly impaired renal function

Other adverse reactions, which occur rarely are:

Body as a whole - anaphylactic reactions, anaphylactoid reactions, appetite changes

Cardiovascular system - arrhythmia, cerebrovascular accident, hypotension, myocardial infarction, palpitations, vasculitis

Digestive system - eructation, gingival ulcer, hepatorenal syndrome, liver necrosis, liver failure, pancreatitis

Hemic and lymphatic system - agranulocystosis, hemolytic anemia, aplastic anemia, lymphadenopathy, neutropenia, pancytopenia

Metabolic and nutritional - hyperglycemia

Nervous system - convulsions, coma, emotional lability hallucinations, aseptic meningitis

Respiratory - apnea, respiratory depression, pneumonia, rhinitis

Skin and appendages - angioedema, toxic epidermal necrosis, erythema multiforme, exfoliative dermatitis, Stevens Johnson syndrome, urticaria, vesiculobullous eruptions

Special senses - amblyopia (blurred and/or diminished vision, scotomata and/or changes in color vision), conjunctivitis, dry eyes, hearing impairment

Urogenital - azotemia, decreased creatinine clearance, glomerulitis, renal papillary necrosis, tubular necrosis

To report SUSPECTED ADVERSE EVENTS, contact Actavis at 1-888-838-2872 or FDA at 1-800-FDA-1088 or http://www.fda.gov/ for voluntary reporting of adverse reactions.

The toxicity of ibuprofen overdose is dependent upon the amount of drug ingested and the time elapsed since ingestion, though individual response may vary, which makes it necessary to evaluate each case individually. Although uncommon, serious toxicity and death have been reported in the medical literature with ibuprofen overdosage. The most frequently reported symptoms of ibuprofen overdose include abdominal pain, nausea, vomiting, lethargy and drowsiness. Other central nervous system symptoms include headache, tinnitus, CNS depression and seizures. Metabolic acidosis, coma, acute renal failure and apnea (primarily in very young children) may rarely occur. Cardiovascular toxicity, including hypotension, bradycardia, tachycardia and atrial fibrillation also have been reported.

The treatment of acute ibuprofen overdose is primarily supportive. Management of hypotension, acidosis and gastrointestinal bleeding may be necessary. In cases of acute overdose, the stomach should be emptied through ipecac-induced emesis or lavage. Emesis is most effective if initiated within 30 minutes of ingestion. Orally administered activated charcoal may help in reducing the absorption and reabsorption of ibuprofen.

In children, the estimated amount of ibuprofen ingested per body weight may be helpful to predict the potential for development of toxicity although each case must be evaluated. Ingestion of less than 100 mg/kg is unlikely to produce toxicity. Children ingesting 100 to 200 mg/kg may be managed with induced emesis and a minimal observation time of four hours. Children ingesting 200 to 400 mg/kg of ibuprofen should have immediate gastric emptying and at least four hours observation in a health care facility. Children ingesting greater than 400 mg/kg require immediate medical referral, careful observation and appropriate supportive therapy. Ipecac-induced emesis is not recommended in overdoses greater than 400 mg/kg because of the risk for convulsions and the potential for aspiration of gastric contents.

In adult patients the history of the dose reportedly ingested does not appear to be predictive of toxicity. The need for referral and follow-up must be judged by the circumstances at the time of the overdose ingestion. Symptomatic adults should be carefully evaluated, observed and supported.

Carefully consider the potential benefits and risks of ibuprofen oral suspension and other treatment options before deciding to use ibuprofen oral suspension. 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 oral suspension, the dose and frequency should be adjusted to suit an individual patient’s needs.

Ibuprofen Oral Suspension USP, 100 mg/5 mL

Orange-colored, berry-flavored suspension

- Bottles of 4 fl oz (118 mL) – NDC 71205-367-72

Shake well before using. Store at 20°C to 25°C (68°F to 77°F). [See USP Controlled Room Temperature.]

Dispense in a well-closed container as defined in the USP.

Manufactured by:

G&W Laboratories, Inc.

South Plainfield, NJ 07080 USA

Distributed by:

Actavis Pharma, Inc.

Parsippany, NJ 07054 USA

Relabeled by:

Proficient Rx LP

Thousand Oaks, CA 91320

Rev. A 3/2019

What is the most important information I should know about medicines called Nonsteroidal Anti-inflammatory Drugs (NSAIDs)?

 NSAIDs can cause serious side effects, including:

 

Increased risk of a heart attack or stroke that can lead to death. This risk may happen early in treatment and may increase:

•

with increasing doses of NSAIDs

•

with longer use of NSAIDs

Do not take NSAIDs right before or after a heart surgery called a “coronary artery bypass graft (CABG)."

 Avoid taking NSAIDs after a recent heart attack, unless your healthcare provider tells you to.

 You may have an increased risk of another heart attack if you take NSAIDs after a recent heart attack.

•

Increased risk of bleeding, ulcers, and tears (perforation) of the esophagus (tube leading from the mouth to the stomach), stomach and intestines:

•

anytime during use

•

without warning symptoms

•

that may cause death

The risk of getting an ulcer or bleeding increases with:

•

past history of stomach ulcers, or stomach or intestinal bleeding with use of NSAIDs

•

taking medicines called “corticosteroids”, “anticoagulants”, “SSRIs”, or “SNRIs”

•

increasing doses of NSAIDs

•

longer use of NSAIDs

•

smoking

•

drinking alcohol

•

older age

•

poor health

•

advanced liver disease

•

bleeding problems

NSAIDs should only be used:

•

exactly as prescribed

•

at the lowest dose possible for your treatment

•

for the shortest time needed

What are NSAIDs?

NSAIDs are used to treat pain and redness, swelling, and heat (inflammation) from medical conditions such as different types of arthritis, menstrual cramps, and other types of short-term pain.

Who should not take NSAIDs?

Do not take NSAIDs:

 

if you have had an asthma attack, hives, or other allergic reaction with aspirin or any other NSAIDs.

 

right before or after heart bypass surgery.

Before taking NSAIDs, tell your healthcare provider about all of your medical conditions, including if you:

 

have liver or kidney problems

 

have high blood pressure

 

have asthma

 

are pregnant or plan to become pregnant. Talk to your healthcare provider if you are considering taking NSAIDs during pregnancy. You should not take NSAIDs after 29 weeks of pregnancy.

 

are breastfeeding or plan to breastfeed.

Tell your healthcare provider about all of the medicines you take, including prescription or

over-the-counter medicines, vitamins or herbal supplements. NSAIDs and some other medicines can interact with each other and cause serious side effects. Do not start taking any new medicine without talking to your healthcare provider first.

What are the possible side effects of NSAIDs?

NSAIDs can cause serious side effects, including:

See “What is the most important information I should know about medicines called Nonsteroidal

Anti-inflammatory Drugs (NSAIDs)?

•

new or worse high blood pressure

•

heart failure

•

liver problems including liver failure

•

kidney problems including kidney failure

•

low red blood cells (anemia)

•

life-threatening skin reactions

•

life-threatening allergic reactions

•

Other side effects of NSAIDs include: stomach pain, constipation, diarrhea, gas, heartburn, nausea, vomiting, and dizziness.

Get emergency help right away if you get 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 taking your NSAID and call your healthcare provider right away if you get any of the following symptoms:

If you take too much of your NSAID, call your healthcare provider or get medical help right away.

These are not all the possible side effects of NSAIDs. For more information, ask your healthcare provider or pharmacist about NSAIDs.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Other information about NSAIDs

•

Aspirin is an NSAID 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 NSAIDs 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.

General information about the safe and effective use of NSAIDs

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use NSAIDs for a condition for which it was not prescribed. Do not give NSAIDs to other people, even if they have the same symptoms that you have. It may harm them.

If you would like more information about NSAIDs, talk with your healthcare provider. You can ask your pharmacist or healthcare provider for information about NSAIDs that is written for health professionals. For more information, call Actavis at 1-888-838-2872.

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

Manufactured by:

G&W Laboratories, Inc.

South Plainfield, NJ 07080 USA

Distributed by:

Actavis Pharma, Inc.

Parsippany, NJ 07054 USA

Relabeled by:

Proficient Rx LP

Thousand Oaks, CA 91320

147I602-1550 GW7234

Rev. 06/17

Rx Only

NDC 71205-367-72

Ibuprofen Oral Suspension, USP

100 mg/5 mL

Dosage Cup Included

PHARMACIST: Dispense the accompanying Medication Guide to each patient.

4 FL OZ (118 mL)