^ .1 Clinical Study Glb -
GLB96-01 was a six month, multi-center, randomized, parallel group, double-blind, placebo-controlled study of prasterone (200mg daily) in Asian women (mean age = 32 years); 97% had baseline SLEDAI score >2. The treatment group (n = 60) had a somewhat higher baseline SLEDAI than did the placebo group (n = 59).
The treatment group significantly had fewer patients with at least one definite flare. The number of patients with definite flares in the treatment group was 46.0% less than in the placebo group (18.3% vs. 33.9%, p = 0.044 based on survival analysis using Cox model).
^ Increased Risk Of Acne And Hirsutism
Acne was the most frequently reported adverse event. Acne was reported less frequently by African American patients, in approximately 26%, compared to approximately 36% in Caucasian patients.
The second most-frequent adverse event was hirsutism. In study GLB96-01 involving patients of Chinese extraction, hirsutism was not reported; this may indicate a decreased racial susceptibility to hirsutism.
Acne and hirsutism were both reversible on cessation of prasterone therapy. In addition, both were more likely to be reported early in treatment; patients who had not developed these within the first 6 months of exposure are less likely to develop them later.
^ .4 Metabolism
Oral prasterone is sulfated to 5-DHEAS ester in the intestine and liver by sulfotransferases. Prasterone and 5-DHEAS are converted in peripheral tissues to androstenedione, androsterone sulfate, estradiol, estriol and estrone, dihydrotestosterone, 7-oxo-prasterone, and testosterone.
^Spl Medguide
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:
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:
The chance of a person getting an ulcer or bleeding increases with:
NSAID medicines should only be used:
What are Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)?
NSAID medicines are used to treat pain and redness, swelling, and heat (inflammation) from medical conditions such as:
Who should not take a Non-Steroidal Anti-Inflammatory Drug (NSAID)?
Do not take an NSAID medicine:
Tell your healthcare provider:
What are the possible side effects of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)?
Get emergency help right away if you have any of the following symptoms:
Stop your NSAID medicine and call your healthcare provider right away if you have any of the following symptoms:
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)
NSAID medicines that need a prescription
*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.
This Medication Guide has been approved by the U.S. Food and Drug Administration.
Manufactured for:Health Science Funding, LLCMorristown, NJ 07960 USA
Manufactured by:Marksans Pharma Ltd. Verna, Goa-403 722, India
Iss. 03/14
^ Description
Prastera® prasterone oral softgels are oblong blue soft gelatin capsules. Each PRASTERA® prasterone oral softgel contains 200mg prasterone (>98% pure), in a lipophilic vehicle.
Prasterone is chemically identical to the naturally-occurring pro-hormone 5-dehydroepiandrosterone, secreted by the adrenal cortex, gonads and brain tissue. It is designated chemically as (3S,8R,9S,10R,13S,14S)-3-hydroxy-10,13-dimethyl-3,4,7,8,9,10,11,12,13,14,15,16 –dodecahydro-1H-cyclopenta[a]phenanthren-17(2H)-one. Its molecular weight is 288.424 g/mol. Its molecular formula is C19H28O2.
^ Other Serious Adverse Events
Adverse events that were assessed as “severe” occurred in similar frequencies in both treatment and placebo groups, with asthenia being the most common adverse event reported as severe in both placebo and treated patients. Although the patient numbers are small, abdominal pain reported as a severe adverse event occurred in 6 treated 200 mg patients, 2 treated 100mg patients, and no placebo patients.
Serious adverse events occurred in 39 200 mg, 7 100 mg, and 47 placebo patients participating in GL94-01 and GL95-02. However, only 3 serious adverse events were considered possibly related, 2 in the placebo group (one suicide and one patient with menomettrorhagia) and one in 200 mg (a patient with an acute psychosis).
In the Taiwan study, serious adverse events were reported in a significantly higher proportion of patients in the placebo group than in the treatment group. In most cases, the types of serious adverse events reported were consistent with SLE flares or hospitalization for manifestations of SLE, rather than adverse effects of the study drug.
^ .2 Absorption
During two weeks of daily administration (200 mg), plasma levels (and times to peak levels) of both 5-dehydroepiandrosterone and its sulfated metabolite did not change significantly in either women or men, indicating a lack of accumulation.
^8 Drug Interactions
There is no known pharmacokinetic effect (bioavailability, pharmacokinetics, or pharmacodynamics) of prasterone on prednisone or hydroxychloroquine, with the possible exception of increasing the magnitude of a decrease in triglycerides seen with hydroxyquinoline.
Prasterone may theoretically interact with one or more of the following drugs: carbamazepine, phenothiazines (e.g., acetophenazine, chlorpromazine, chlorprothixene, ethopropazine, fluphenazine, mesordiazine, methdilazine, perazine, perphenazine, pipotiazine, prochlorperazine, promazine, promethazine, propiomazine, thioridazine, trifluoperazine, triflupromazine), citalopram; escitalopram; clozapine, conjugated estrogens; estherified estrogens; estradiol; estradiol cypionate; estropipate; ethinyl estradiol, fluoxetine, fluvoxamine; haloperidol, lithium, loxapine, molindone, olanzapine, paroxetine, quetiapine, risperodone, sertraline, testosterone, triazolam and valproic acid. For further information on potential interactions with these drugs, please see The Cochrane Review monograph for prasterone.
^ Athletic Anti-doping
Prasterone use is prohibited by certain athletic anti-doping regulations.
^ Patients With Active Sle Disease
The GL94-01 and GL95-02 clinical studies showed a difference in responder rates between placebo and prasterone increased with increasing baseline SLEDAI.
^ Benefits
Oral prasterone 200 mg / day reduced the risk of auto-immune flare, §§6.2, 14.1, and significantly reduced the risk of death, §§6.4, 14.2, in placebo-controlled, randomized, blinded clinical studies (GL94-01, GL95-01, GL95-02 and GLB96-01) in female patients with Systemic Lupus Erythematosus. Results observed in clinical trials may not, however, reflect the rates observed in practice.
PRASTERA® does not cure, mitigate, treat or prevent the patient's underlying SLE. To the contrary, the patient will continue to have SLE. The patient therefore should continue to be monitored by a physician and should continue other therapy (e.g., prednisone, NSAID) as believed appropriate.
Oral prasterone reduced the risk of auto-immune flare and death. See above. PRASTERA® may not, however, make the patient feel significantly different on a day-to-day basis. This does not mean PRASTERA® is not working; it may take at least six months of continuous therapy to achieve a statistically-significant reduction in risk of flare and death. §14.
^ .1 Clinical Study Gl -
Study GL94-01 compared the proportion of patients achieving sustained reduction of daily corticosteroid dose, without worsening of signs and symptoms of SLE (“Responders”), in placebo (n = 64) and prasterone 200 mg (n = 64) groups for about 7 months.
For all randomized patients, 26/64 (41%) placebo and 35/64 (55%) prasterone 200 mg patients responded: a strong trend in favor of prasterone (p = 0.110). For patients with baseline SLEDAI >2, 13/45 (29%) placebo and 23/45 (51%) prasterone 200mg patients responded (p = 0.031).
^ Clinical Laboratory Evaluation
In the placebo-controlled trials, testosterone was increased in a dose related manner in SLE patients receiving prasterone.
Prasterone caused an increased number of patients (in comparison to placebo) to have a decrease in serum complement (C3). The decrease in C3 was not associated with renal dysfunction. The medical literature suggests that a decline in serum complement may be a direct effect of suppression of complement production by androgens.
The clinical studies suggest that administration of prasterone causes an early, but not progressive, decrease in serum lipids, primarily HDL-C and triglycerides. It would be prudent to follow NCEP guidelines while monitoring lipids in patients receiving prasterone.
There were no changes of potential significance in liver function tests (ALT, AST, alkaline phosphatase, or total bilirubin) within and between the treatment groups. Equally, serum calcium, phosphorus, uric acid, total protein and albumin showed no clinically relevant differences.
Mean 24-hour urine protein excretion was slightly higher in the prasterone group viz placebo.
There does not appear to be a difference between placebo and prasterone for new hematuria accompanied by SLE renal involvement, as manifested by changes in urinary protein excretion, increased creatinine, or new therapy for renal SLE.
^4 Contraindications
Prastera® oral softgels should not be used in patients with any of the following conditions:
^ Pregnancy
Instruct patients who are nursing, pregnant or intending to become pregnant, not to use PRASTERA®.
^ Relationship Of Dose To Safety
Neither adverse events nor laboratory values showed a dose relationship.
^ How Supplied / Dosage And Handling
Prastera® softgels 200mg are oblong blue soft, liquid filled gelatin capsules.
Store at not more than 25° C (77° F). Excursions are permitted to 15° C to 30° C (59° F to 86° F). See United States Pharmacopoeia, Controlled Room Temperature. Protect from excessive moisture or humidity. Dispense in a tight, light-resistant container as defined in USP/NF, using a child-resistant closure system, accompanied by a Patient Insert and in a convenience pack together with a blister strip of ibuprofen 400mg oral tablets.
NDC 55607-400-10
Keep out of reach of children.
^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 μg/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 μg/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.
^ Pre-clinical Toxicology
The non-clinical literature indicates that prasterone may be either chemo-protective or carcinogenic, depending on the model. Prasterone may thus be inhibitory or stimulatory to hormone-senentive tumors. The literature, however, suggests that prasterone is less potent than its androgenic and estrogenic metabolites. Similarly to androgenic and extrogenic compounds, it is expected to be difficult to define the carcinogenic potential of prasterone.
^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.
^ Clinical Studies
The placebo-controlled studies (GL94-01, GL95-01, GL95-02 and GLB96-01) had very different study designs and efficacy endpoints. Pooling of efficacy data is thus not meaningful. Consequently, results are presented by individual study.
^ Special Precautions
None.
^ Patient Counseling Information
See Medication Guide (§17) for specific patient instructions.
^ Reduced Risk Of Myalgia And Other Flare Symptoms
Placebo-treated patients had higher incidences of myalgia, joint disorder, anorexia, nasal ulcers and LE skin rash than did prasterone-treated patients. These differences may be due to the decreased risk of flare observed in prasterone-treated patients. §14.1.
^ .6 Special Populations
The pharmacokinetics of oral prasterone has not been assessed in low body weight or obese patients. There is insufficient information available from placebo-controlled clinical trials to compare prasterone pharmacokinetics in different racial groups, nor for patients with renal or hepatic impairment.
^ .5 Excretion
Prasterone (200mg dose) elimination half-life: young women, 11 hours; elderly men, 7 hours. In elderly women, the elimination half-life progressively declined, from about 12 hours (day 1), to 9 hours (day 8), to 7 hours (day 15). 5-DHEAS half-life: young women, 12 hours; elderly men, 20-25 hours; elderly women, 24-27 hours.
^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 (< 1 mg/mL) and readily soluble in organic solvents such as ethanol and acetone . The structural formula is represented below:
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.
^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 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.
^ Allergy Warning
Prastera® oral softgels contain soy oil and soy lecithin. No milk, eggs, fish, crustacean shellfish, tree nuts, wheat, peanuts.
^ Reduced Risk Of Death
In the GL94-01, GL95-01 and GL95-02 placebo-controlled clinical studies (pooled data), the placebo group experienced 6 deaths in 77 patients, a risk of death of 7.8%. In contrast, the prasterone group (pooled treatment and cross-over) experienced 8 deaths in 495 patients, a risk of death of 1.6%. The risk of death from any cause was therefore five times higher in the placebo group.
^Principal Display Panel - Capsule Label
Prasterone 200mg
Contents: 15 softgels.
Directions: One softgel daily.
^ Post-marketing Experience
The following adverse reactions have been reported with unregulated dietary supplements containing DHEA. The identity, purity and strength of the product used was not always known. It is therefore not possible to establish a causal relation to prasterone exposure.
Cardiovascular Effects: Benign premature atrial contractions and occasional premature ventricular contractions occurred in a 55-year-old man after administration of DHEA; DHEA was discontinued and arrhythmias controlled by beta-blockers. (Sahelian 1998)
One case of hepatitis has been reported in a patient with high pre-treatment anti-nuclear antibody (ANA) titers; causality is uncertain. (Buster 1992)
Manic reactions during DHEA use have been described. (Dean 2000; Pies 2000) Risk factors for development of mania / psychosis are considered to be higher doses, combined use with antidepressants, alcohol or benzodiazepines, young patients (20-30 years, with peak endogenous DHEA levels), and cytochrome P450 polymorphisms (poor metabolizers).
^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 other side)
Blister strips of 5 (NDC 55607-400-10)
Store at controlled room temperature 20° to 25°C (68° to 77°F) [see USP].
Rx only
Manufactured for:Health Science Funding, LLCMorristown, NJ 07960 USA
Manufactured by:Marksans Pharma Ltd. Verna, Goa-403 722, India
Iss. 03/14
^ Other Common Adverse Events
No adverse events increase in frequency with longer duration of treatment. The Table displays all adverse events reported in a frequency of 10% or greater from either the 200 mg dose group or the placebo group for the pooled double-blind phases of Studies GL94-01 and GL95-02. Because the number of patients who received prasterone 100 mg was substantially fewer, adverse events for this group are only presented for those adverse events which were reported in≥ 10% of either placebo or prasterone 200 mg patients.
For adverse events occurring in < 10% of patients, the following showed an absolute difference of at least 3% between placebo or prasterone 200 mg, or, if less than 3% difference, the difference was significant (p < 0.05):
The pattern of adverse events in clinical study GLB96-01 showed a similar, but not identical pattern. Acne was the most common adverse event; this may reflect the fact that almost all patients were also receiving corticosteroids. This may also reflect racial differences in sensitivity to prasterone. By contrast, hirsutism was not reported at all in GLB96-01.
Of adverse events reported by at least 10% of patients, acne was the only event significantly more frequent in the treatment group. Headache and infection were more frequent in the placebo group. Of the adverse events reported with an incidence of less than 10%, the only statistically significant difference was for seborrhea (0 placebo vs. 5 treatment patients).
^ Males
The placebo-controlled, double-blind clinical studies involved women. Use in men at this time is not recommended because data is lacking.
^ .2 Clinical Study Gl -
Study GL95-02 was a 12 month, multi-center, randomized, parallel group, double-blind, placebo-controlled study of prasterone (200mg daily) in women (n = 346) with active SLE (SLAM score≥7 excluding ESR, SLEDAI score >2) receiving≤10 mg/day prednisone (or its equivalent of other cortico-steroids). A secondary efficacy variable (flare) was defined as a modified SELENA definition flare.
Three hundred eighty one (381) patients were randomized, of whom 346 were in the per-protocol population. For all patients, 47/176 (27%) of placebo and 37/170 (22%) of prasterone patients experienced a definite flare.
For the subset of patients with a baseline SLEDAI>2, treated patients had a 23.7% decrease in the risk of experiencing at least one definite flare, compared to placebo. During the study period, 41/133 (31%) of placebo patients and 31/132 (23.5%) of prasterone patients experienced a definite flare. See bar chart.
For patients with a baseline SLEDAI>2, treated patients had a 23.7% decrease in the risk of experiencing at least one definite flare, compared to placebo (p=0.201, log-rank test for time to first definite flare).
^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 ).
^ Patient / Caregiver Instructions
Inform patients of the following information before initiating therapy with PRASTERA® and periodically during the course of on-going therapy. Encourage patients to read the Medication Guide that accompanies each prescription dispensed, prior to using PRASTERA®.
^3 Dosage Forms And Strengths
Prastera® oral prasterone is provided as oral softgels. Each softgel contains 200mg of prasterone (≥99% pure). Other ingredients: soybean oil USP, soy lecithin NF, gelatin NF, beeswax USP, titanium dioxide USP, polysorbate 80, silicon dioxide, FD&C Blue.
^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 been 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< .001).
Gastroscopic 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 51Cr-tagged red 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 significant 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 ibuprofen 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 proportional to increases in dose. There is no evidence of drug accumulation or enzyme induction.
The administration 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 bioavailability of the drug is minimally altered by the presence of food.
A bioavailability 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 rapidly 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%), (+)-2-[p-(2carboxypropyl)phenyl] propionic acid; the percentages of free and conjugated ibuprofen were approximately 1%and 14%, respectively.
^ Medication Guide
^ Adverse Reactions
PRASTERA® may cause acne. This acne is reversible on cessation of prasterone therapy, and may be treateable by a topical anti-acne drug. You may request a Prastera® convenience kit which includes a topical anti-acne drug.
PRASTERA® may cause hirsutism, reversible on cessation of prasterone therapy.
PRASTERA® may cause hypertension, §6.3.2, and/or changes in serum lipids, §7.2.4, or serum hormone levels, §7.2.1. These should be monitored, and are reversible on cessation of prasterone therapy.
^ Clinical Pharmacology
Prastera® softgels are an oral dosage form of pharmaceutical-grade prasterone, chemically identical to prasterone of native human origin, in a lipophilic vehicle.
^ General Instructions
The recommended dose is one 200mg oral softgel daily, with or without food.
^ .1 Time To Peak Concentration
Oral prasterone reaches a peak serum concentration at 1.5 to 2 hours after administration. In healthy young women (mean age, 30 years) receiving prasterone 200 mg daily (given with prednisone), mean peak plasma levels on day 29 of prasterone and 5-DHEAS were 1.3 mcg/dL (13 ng/mL) and 942 mcg/dL (9.4 mcg/mL), and occurred in 2 hours and 2.4 hours, respectively, after administration. In elderly women (mean, 69 years) and elderly men (mean, 69 years), mean peak plasma concentrations (times to peak levels) after a single 200-mg micronized oral dose were 27 ng/mL (1.4 hours) and 22 ng/mL (1.3 hours), respectively. After a single 200 mg dose, mean serum levels of 5-DHEAS increased 5-fold in men (to 7 mcg/mL) and 21-fold in women (to 7.5 mcg/mL) relative to baseline healthy levels.
^Principal Display Panel - Blister Label
NDC 55607-400-10
Rx Only
Prastera®
IbuprofenTablets USP
400 mg
5 tablets
Health ScienceFunding LLC
^ Reduction In Risk Of Death
In the GL95-02 study (discussed above), five placebo patients died, and no prasterone-treated patients died. These data show a statistically significant and clinically meaningful reduction in risk of death by any cause. In the GL94-01, GL95-01 and GL95-02 clinical trials (pooled data), the prasterone treated group (including prasterone-treated crossover patients) experienced 8 deaths among 495 patients, or a risk of death of 1.62%. In contrast, the placebo group experienced 6 deaths among 77 patients, or a risk of death of 7.80%.
^ .1 Hypertension
Hypertension was reported as an adverse event more frequently in the prasterone 200 mg group than placebo. When measures of increased (changed) blood pressure were included, there appeared to be no difference between the groups. Whether prasterone increases hypertension is thus not clear.
^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 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.
^Principal Display Panel - Kit Label
Prastera® Kit
Rx only.
Keep away from children.
See package inserts forcomplete prescribingand use information
NDC 55607-400-10
Kit includes:
^6 Adverse Reactions
The most-frequent adverse reactions observed in placebo-controlled, blinded clinical studies GL94-01, GL95-01, GL95-02 and GLB96-01 are as follows:
^ Other Medications
PRASTERA® is a synthetic form of 5-dehydroepiandrosterone. PRASTERA® should not be combined with dietary supplements containing “DHEA” or “dehydroepiandrosterone.”
PRASTERA® is a precursor to testosterone and estrogens. If PRASTERA® is used in conjunction with testosterone or estrogens, levels of serum testosterone and estrogens should be monitored closely to assure levels do not exceed the range seen in healthy women of similar age.
^ .3 Distribution
Approximately 10% to 20% of prasterone is bound to serum protein; approximately 80% to 90% of 5-DHEAS is bound to protein. 5-DHEAS penetrates the blood-brain barrier; cerebro-spinal fluid levels of 5-DHEAS range from 0.2% to 5% of corresponding plasma levels.
^5 Warnings And Precautions
PRASTERA® is not intended for use in children, nor males, nor women who are breastfeeding, pregnant, or who expect to become pregnant. §9. Monitoring of blood pressure, serum lipids, serum sex hormones is prudent. See Clinical Laboratory Evaluation, §§7.2.1, 7.2.4.
^ Overdose
Oral prasterone of up to 1.6 grams per day has not provoked overdose in post-menopausal women. (Mortola 2000) In case of suspected overdose, Prastera® softgels should be discontinued and the patient should be treated symptomatically.
^ Pediatric Use
Safety and effectiveness in pediatric patients have not been established. Use in pediatric patients is not recommended.
^ Pregnancy
Safety and effectiveness in nursing and pregnant women has not been established. Use is not recommended.
^1 Indications And Usage
Oral prasterone (200mg per day) in female patients with active systemic lupus erythematosus (SLE) has in several blinded, placebo-controlled randomized clinical studies been associated with a reduced risk of auto-immune flare, §§6.2, 14.1.1, a reduced risk of breast cancer and a reduced risk of death from any cause, §§6.4, 14.2.
Patients with SLE may have depressed serum levels of 5-dehydroepiandrosterone sulfate (5-DHEAS). Oral prasterone has been shown to restore SLE patients' serum 5-DHEAS levels. Prastera® oral softgels are intended for use in patients for whom medical evaluation shows a depressed serum level of DHEA and thus a distinctive need for exogenous DHEA. Prastera® oral prasterone softgels are intended to be used under medical supervision, for a patient receiving active and ongoing medical supervision, wherein the patient obtains medical care on a recurring basis for, among other things, instructions on the use of this product. Prastera® oral prasterone softgels are intended for the dietary management of SLE by meeting the distinctive nutritional requirement of women with mild-to-moderate active SLE. Prastera® oral prasterone softgels are intended for oral intake only.
Prastera® does not cure, treat, mitigate or prevent SLE. To the contrary, patients taking Prastera® will continue to have SLE, and thus may continue to require other appropriate therapy.
^Boxed Warning
Cardiovascular Risk
Gastrointestinal Risk
^ Pharmacodynamics
Oral prasterone has been shown to increase serum levels of 5-DHEAS. The precise mechanism by which normal serum levels of 5-DHEAS may act to reduce the risk of auto-immune flare, breast cancer and death is not known.
^ Reduced Risk Of Breast Cancer
In the GL94-01, GL95-01 and GL95-02 placebo-controlled clinical studies (pooled data), incidence of breast cancer was 1 in 336 patient-years (0.29%) for placebo and 3 in 1573 patient-years (0.19%) for prasterone (pooled treatment and cross-over). Prasterone was thus associated with reducing the risk of breast cancer by one third.
For patients over 44 years of age, the difference between placebo and prasterone groups was more pronounced. For women at least 45 years of age, the rate of breast cancer was 1 in 24 patient-years (4.2%) for placebo and 3 in 206 patient-years (1.5%) for prasterone treatment and cross-over patients. Prasterone was thus associated with reducing the risk of breast cancer by two thirds.