LURBIPR- flurbiprofen_tablet

Flurbiprofen has analgesic, anti-inflammatory, and antipyretic properties. The mechanism of action of flurbiprofen, like that of other NSAIDs, is not completely understood but involves inhibition of cyclooxygenase (COX-1 and COX-2). Flurbiprofen is a potent inhibitor of prostaglandin (PG) synthesis in vitro. Flurbiprofen concentrations reached during therapy have produced in vivo effects. Prostaglandins sensitize afferent nerves and potentiate the action of bradykinin in inducing pain in animal models. Prostaglandins are mediators of inflammation. Because flurbiprofen is an inhibitor of prostaglandin synthesis, its mode of action may be due to a decrease of prostaglandins in peripheral tissues. General pharmacokinetic characteristics The pharmacokinetics of flurbiprofen have been characterized in healthy subjects, special populations and patients (see Table 2 Table 2 :Mean (SD) R-, S-Flurbiprofen Pharmacokinetic Parameters Normalized to a 100 mg Dose of Flurbiprofen Tablets Pharmacokinetic Parameter Normal Healthy Adults 100 mg single-dose Geriatric Arthritis Patients Steady-state evaluation of 100 mg every 12 hours End Stage Renal Disease Patients Alcoholic Cirrhosis Patients 200 mg single-dose Peak Concentration 14 (4) 16 (5) 9 Calculated from mean parameter values of both flurbiprofen enantiomers 9 Time to Reach Peak Concentration (h) 1. 2 Urinary Recovery of Unchanged Flurbiprofen 2. 02) NA Not available Area Under the Curve (AUC) AUC from 0 to infinity for single doses and from 0 to the end of the dosing interval for multiple-doses 83 (20) 77 (24) 44 50 Apparent Volume of Distribution 14 (3) 12 (5) 10 14 Terminal Elimination Half-life ½ 7. 3 Value for S-flurbiprofen 5. 4 Absorption The mean oral bioavailability of flurbiprofen from flurbiprofen tablets 100 mg is 96% relative to an oral solution. Flurbiprofen is rapidly and non-stereoselectively absorbed from flurbiprofen, with peak plasma concentrations occurring at approximately 2 hours (see Table 2 Administration of flurbiprofen with either food or antacids may alter the rate but not the extent of flurbiprofen absorption. Ranitidine has been shown to have no effect on either the rate or extent of flurbiprofen absorption from flurbiprofen. Distribution The apparent volume of distribution (Vz/F) of both R- and S-flurbiprofen is approximately 0. Both flurbiprofen enantiomers are more than 99% bound to plasma proteins, primarily albumin. Plasma protein binding is relatively constant for the typical average steady-state concentrations (<= 10 mcg/mL) achieved with recommended doses. Flurbiprofen is poorly excreted into human milk. The nursing infant dose is predicted to be approximately 0. 1 mg/day in the established milk of a woman taking flurbiprofen 200 mg/day. Metabolism Several flurbiprofen metabolites have been identified in human plasma and urine. These metabolites include 4'-hydroxy-flurbiprofen, 3', 4'-dihydroxy-flurbiprofen, 3'-hydroxy-4'-methoxy-flurbiprofen, their conjugates, and conjugated flurbiprofen. Unlike other arylpropionic acid derivatives (e. , ibuprofen), metabolism of R-flurbiprofen to S-flurbiprofen is minimal. In vitro studies have demonstrated that cytochrome CYP2C9 plays an important role in the metabolism of flurbiprofen to its major metabolite 4'-hydroxy-flurbiprofen. The 4'-hydroxy-flurbiprofen metabolite showed little anti-inflammatory activity in animal models of inflammation. In vitro studies also demonstrated glucuronidation of both enantiomers of flurbiprofen and 4'-hydroxy-flurbiprofen. UGT2B7 is the predominant UGT isozyme responsible for the glucuronidation. Flurbiprofen does not induce enzymes that alter its metabolism. Excretion Following dosing with flurbiprofen, less than 3% of flurbiprofen is excreted unchanged in the urine, with about 70% of the dose eliminated in the urine as flurbiprofen, 4'-hydroxy-flurbiprofen, and their acylglucuronide conjugates. Because renal elimination is a significant pathway of elimination of flurbiprofen metabolites, dosing adjustment in patients with moderate or severe renal dysfunction may be necessary to avoid accumulation of flurbiprofen metabolites. The mean terminal elimination half-lives (t ½ Specific Populations Pediatric: Race: Geriatric: Hepatic Impairment: Renal Impairment: Flurbiprofen is not significantly removed from the blood into dialysate in patients undergoing continuous ambulatory peritoneal dialysis. Drug Interaction Studies Antacids: Administration of flurbiprofen to volunteers under fasting conditions or with antacid suspension yielded similar serum flurbiprofen-time profiles in young adult subjects (n = 12). In geriatric subjects (n = 7), there was a reduction in the rate but not the extent of flurbiprofen absorption. Aspirin: Concurrent administration of flurbiprofen and aspirin resulted in 50% lower serum flurbiprofen concentrations. This effect of aspirin (which is also seen with other NSAIDs) has been demonstrated in patients with rheumatoid arthritis (n = 15) and in healthy volunteers (n = 16) [ see Drug Interactions (7) Beta-adrenergic Blocking Agents: The effect of flurbiprofen on blood pressure response to propranolol and atenolol was evaluated in men with mild uncomplicated hypertension (n = 10). Flurbiprofen pretreatment attenuated the hypotensive effect of a single dose of propranolol but not atenolol. Flurbiprofen did not appear to affect the beta-blocker-mediated reduction in heart rate. Flurbiprofen did not affect the pharmacokinetic profile of either drug [ see Drug Interactions (7) Cimetidine, Ranitidine: In normal volunteers (n = 9), pretreatment with cimetidine or ranitidine did not affect flurbiprofen pharmacokinetics, except for a small (13%) but statistically significant increase in the area under the serum concentration curve of flurbiprofen in subjects who received cimetidine. Digoxin: In studies of healthy males (n = 14), concomitant administration of flurbiprofen and digoxin did not change the steady state serum levels of either drug [ see Drug Interactions (7) Diuretics: Studies in healthy volunteers have shown that, like other NSAIDs, flurbiprofen can interfere with the effects of furosemide. Although results have varied from study to study, effects have been shown on furosemide-stimulated diuresis, natriuresis, and kaliuresis [ see Drug Interactions (7) Lithium: In a study of 11 women with bipolar disorder receiving lithium carbonate at a dosage of 600 to 1200 mg/day, administration of 100 mg flurbiprofen every 12 hours increased plasma lithium concentrations by 19%. Four of 11 patients experienced a clinically important increase (> 25% or > 0. 2 mmol/L) [ see Drug Interactions (7) Methotrexate: In a study of six adult arthritis patients, coadministration of methotrexate (10 to 25 mg/dose) and flurbiprofen (300 mg/day) resulted in no observable interaction between these two drugs [ see Drug Interactions (7) Oral Hypoglycemic Agents: In a clinical study, flurbiprofen was administered to adult diabetics who were already receiving glyburide (n = 4), metformin (n = 2), chlorpropamide with phenformin (n=3), or glyburide with phenformin (n = 6). Although there was a slight reduction in blood sugar concentrations during concomitant administration of flurbiprofen and hypoglycemic agents, there were no signs or symptoms of hypoglycemia. Poor Metabolizers of CYP2C9 Substrates: In patients who are known or suspected to be poor CYP2C9 metabolizers based on genotype or previous history/experience with other CYP2C9 substrates (such as warfarin and phenytoin), reduce the dose of flurbiprofen to avoid abnormally high plasma levels due to reduced metabolic clearance.

LURBIPR TM For relief of the signs and symptoms of rheumatoid arthritis. For relief of the signs and symptoms of osteoarthritis. LURBIPR TM Relief of the signs and symptoms of rheumatoid arthritis ( 1 Relief of the signs and symptoms of osteoarthritis ( 1.

Carefully consider the potential benefits and risks of flurbiprofen tablets and other treatment options before deciding to use flurbiprofen tablets. Use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals [ see Warnings and Precautions (5. 9) After observing the response to initial therapy with flurbiprofen tablets, the dose and frequency should be adjusted to suit an individual patient's needs. For relief of the signs and symptoms of rheumatoid arthritis or osteoarthritis, the dosage is 200 to 300 mg per day, divided for administration two, three, or four times a day. The largest recommended single dose in a multiple-dose daily regimen is 100 mg. Use the lowest effective dosage for shortest duration consistent with individual patient treatment goals ( 2 The recommended starting dose of flurbiprofen tablets is 200 to 300 mg per day, divided for administration two, three, or four times a day. The largest recommended single dose in a multiple-dose daily regimen is 100 mg ( 2.

The following adverse reactions are discussed in greater detail in other sections of the labeling: Cardiovascular Thrombotic Events [ see Warnings and Precautions (5. 1) GI Bleeding, Ulceration and Perforation [ see Warnings and Precautions (5. 2) Hepatotoxicity [ see Warnings and Precautions (5. 3) Hypertension [ see Warnings and Precautions (5. 4) Heart Failure and Edema [ see Warnings and Precautions (5. 5) Renal Toxicity and Hyperkalemia [ see Warnings and Precautions (5. 6) Anaphylactic Reactions [ see Warnings and Precautions (5. 7) Serious Skin Reactions [ see Warnings and Precautions (5. 9) Hematologic Toxicity [ see Warnings and Precautions (5. 12) Most common adverse reactions (incidence > 3% from clinical trials) are: abdominal pain, dyspepsia, nausea, diarrhea, constipation, headache, edema, signs and symptoms suggesting urinary tract infection ( 6. 1 To report SUSPECTED ADVERSE REACTIONS, contact New HeightsRx, LLC at 1-888-322-4106 or FDA at 1-800-FDA-1088 or http://www. gov/medwatch for voluntary reporting of adverse reactions. Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Incidence of 1% or greater Body as a whole: Digestive system: Metabolic and nutritional system: Nervous system: Respiratory system: Skin and appendages: Special senses: Urogenital system: Incidence < 1 % Body as a whole: Cardiovascular system: Digestive system: Hemic and lymphatic system: Metabolic and nutritional system: Nervous system: Respiratory system: Skin and appendages: Special senses: Urogenital system: The following adverse reactions have been identified during post approval use of flurbiprofen. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Cardiovascular system: Digestive system: Hemic and lymphatic system: Metabolic and nutritional system: Nervous system: Respiratory system: Skin and appendages: Special senses: Urogenital system:.

LURBIPR TM Known hypersensitivity (e. , anaphylactic reactions and serious skin reactions) to flurbiprofen or any components of the drug product [ see Warnings and Precautions (5. 9) History of asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs. Severe, sometimes fatal, anaphylactic reactions to nonsteroidal anti-inflammatory drugs have been reported in such patients [ see Warnings and Precautions (5. 8) In the setting of coronary artery bypass graft (CABG) surgery [ see Warnings and Precautions (5. 1) Known hypersensitivity to flurbiprofen or any components of the drug product ( 5. 9 History of asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs ( 5. 8 In the setting of CABG surgery ( 5.

Infertility 8. 3 See 17 for PATIENT COUNSELING INFORMATION and Medication Guide Risk Summary Use of NSAIDs, including flurbiprofen tablets, can cause premature closure of the fetal ductus arteriosus and fetal renal dysfunction leading to oligohydramnios and, in some cases, neonatal renal impairment. Because of these risks, limit dose and duration of flurbiprofen tablets use between about 20 and 30 weeks of gestation, and avoid flurbiprofen tablets use at about 30 weeks of gestation and later in pregnancy [ see Clinical Considerations Data Premature Closure of Fetal Ductus Arteriosus Use of NSAIDs, including flurbiprofen tablets, at about 30 weeks gestation or later in pregnancy increases the risk of premature closure of the fetal ductus arteriosus. Oligohydramnios/Neonatal Renal Impairment Use of NSAIDs at about 20 weeks gestation or later in pregnancy has been associated with cases of fetal renal dysfunction leading to oligohydramnios, and in some cases, neonatal renal impairment. Data from observational studies regarding potential embryofetal risks of NSAID use in U. population, all clinically recognized pregnancies, regardless of drug exposure, women in the first or second trimesters of pregnancy are inconclusive. In the general have a background rate of 2 to 4% for major malformations, and 15 to 20% for pregnancy loss. In animal reproduction studies, delayed parturition, prolonged labor, stillborn fetuses, and the presence of retained fetuses at necropsy occurred following treatment of pregnant rats treated with oral flurbiprofen throughout gestation until labor at less than 1-time the human dose of 300 mg/day. Embryofetal lethality was seen in pregnant rats and rabbits administered oral flurbiprofen during the period of organogenesis at exposures 0. 03-times and 0. 5 times, respectively, the human dose of 300 mg. No evidence of malformations were noted in rats, rabbits, or mice treated with flurbiprofen during the period of organogenesis at doses that were 0. 2-times the maximum human daily dose [ see Data Clinical Considerations Fetal/Neonatal Adverse Reactions Premature Closure of Fetal Ductus Arteriosus: Avoid use of NSAIDs in women at about 30 weeks gestation and later in pregnancy, because NSAIDs, including flurbiprofen tablets, can cause premature closure of the fetal ductus arteriosus [ see Data Oligohydramnios/Neonatal Renal Impairment If an NSAID is necessary at about 20 weeks gestation or later in pregnancy, limit the use to the lowest effective dose and shortest duration possible. If flurbiprofen tablets treatment extends beyond 48 hours, consider monitoring with ultrasound for oligohydramnios. If oligohydramnios occurs, discontinue flurbiprofen tablets and follow up according to clinical practice [ see Data Data Human Data Premature Closure of Fetal Ductus Arteriosus: Published literature reports that the use of NSAIDs at about 30 weeks of gestation and later in pregnancy may cause premature closure of the fetal ductus arteriosus. Oligohydramnios/Neonatal Renal Impairment: Published studies and postmarketing reports describe maternal NSAID use at about 20 weeks gestation or later in pregnancy associated with fetal renal dysfunction leading to oligohydramnios, and in some cases, neonatal renal impairment. These adverse outcomes are seen, on average, after days to weeks of treatment, although oligohydramnios has been infrequently reported as soon as 48 hours after NSAID initiation. In many cases, but not all, the decrease in amniotic fluid was transient and reversible with cessation of the drug. There have been a limited number of case reports of maternal NSAID use and neonatal renal dysfunction without oligohydramnios, some of which were irreversible. Some cases of neonatal renal dysfunction required treatment with invasive procedures, such as exchange transfusion or dialysis. Methodological limitations of these postmarketing studies and reports include lack of a control group; limited information regarding dose, duration, and timing of drug exposure; and concomitant use of other medications. These limitations preclude establishing a reliable estimate of the risk of adverse fetal and neonatal outcomes with maternal NSAID use. Because the published safety data on neonatal outcomes involved mostly preterm infants, the generalizability of certain reported risks to the full-term infant exposed to NSAIDs through maternal use is uncertain. Animal data Pregnant rats were treated with oral doses of 0. 05, 1, and 3 mg/kg flurbiprofen 14 days prior to mating through Gestation Day (GD) 16. Embryofetal lethality was seen at 1 mg/kg and above (0. 03 times the maximum recommended human dose [MRHD] of 300 mg on a mg/m 2 2 Pregnant rabbits were administered oral doses of 0. 5 mg/kg flurbiprofen from GD 1 through GD 29. Embryofetal lethality, but no evidence of teratogenicity, was seen at 7. 5 times the MRHD of 300 mg on a mg/m 2 Pregnant mice were treated with oral doses of 2, 5, and 12 mg/kg flurbiprofen from GD 3 to 18. An increased incidence of fetal lethality occurred in the 12 mg/kg group (0. 2 times the MRHD). All doses were associated with some evidence of maternal toxicity (placental hemorrhage). Pregnant rats were treated with oral doses of 0. 5, and 25 mg/kg flurbiprofen from GD 1 until labor. Delayed delivery, the incidence of stillborn pups, and decreased pup viability, were noted at doses of 2. 25 mg/kg and higher (0. 07 times the MRHD). These doses were associated with maternal toxicity (uterine hemorrhage, gastrointestinal ulceration, decreased body weight). Pregnant rats treated with oral doses of 0. 4, 4, and 10 mg/kg flurbiprofen from GD 16 to labor, delayed parturition was seen at 0. 4 mg/kg and above and stillborn pups were seen at 4 mg/kg and above (0. 01-times and 0. 13 times, respectively, the MRHD on mg/m 2 Labor or Delivery There are no studies on the effects of flurbiprofen during labor or delivery. In animal studies, NSAIDS, including flurbiprofen, inhibit prostaglandin synthesis, cause delayed parturition, and increase the incidence of stillbirth. Risk Summary Flurbiprofen is poorly excreted into human milk. The nursing infant dose is predicted to be approximately 0. 1 mg/day in the established milk of a woman taking flurbiprofen 200 mg/day. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for flurbiprofen and any potential adverse effects on the breastfed infant from flurbiprofen or from the underlying maternal condition. Infertility Females Based on the mechanism of action, the use of prostaglandin-mediated NSAIDs, including flurbiprofen, may delay or prevent rupture of ovarian follicles, which has been associated with reversible infertility in some women. Published animal studies have shown that administration of prostaglandin synthesis inhibitors has the potential to disrupt prostaglandin-mediated follicular rupture required for ovulation. Small studies in women treated with NSAIDs have also shown a reversible delay in ovulation. Consider withdrawal of NSAIDs, including flurbiprofen, in women who have difficulties conceiving or who are undergoing investigation of infertility. Safety and effectiveness in pediatric patients have not been established. Elderly patients, compared to younger patients, are at greater risk for NSAID-associated serious cardiovascular, gastrointestinal, and/or renal adverse reactions. If the anticipated benefit for the elderly patient outweighs these potential risks, start dosing at the low end of the dosing range, and monitor patients for adverse effects [ see Warnings and Precautions (5.

See Table 1 Table 1: Clinically Significant Drug Interactions with Flurbiprofen Drugs That Interfere with Hemostasis Clinical Impact: Flurbiprofen and anticoagulants such as warfarin have a synergistic effect on bleeding. The concomitant use of flurbiprofen and anticoagulants have an increased risk of serious bleeding compared to the use of either drug alone. Serotonin release by platelets plays an important role in hemostasis. Case-control and cohort epidemiological studies showed that concomitant use of drugs that interfere with serotonin reuptake and an NSAID may potentiate the risk of bleeding more than an NSAID alone. Intervention: Monitor patients with concomitant use of flurbiprofen with anticoagulants (e. , warfarin), antiplatelet agents (e. , aspirin), selective serotonin reuptake inhibitors (SSRIs), and serotonin norepinephrine reuptake inhibitors (SNRIs) for signs of bleeding [ see Warnings and Precautions (5) Aspirin Clinical Impact: Controlled clinical studies showed that the concomitant use of NSAIDs and analgesic doses of aspirin does not produce any greater therapeutic effect than the use of NSAIDs alone. In a clinical study, the concomitant use of an NSAID and aspirin was associated with a significantly increased incidence of GI adverse reactions as compared to use of the NSAID alone [ see Warnings and Precautions (5) Intervention: Concomitant use of flurbiprofen and analgesic doses of aspirin is not generally recommended because of the increased risk of bleeding [ see Warnings and Precautions (5) ACE Inhibitors, Angiotensin Receptor Blockers, and Beta-Blockers Clinical Impact: NSAIDs may diminish the antihypertensive effect of angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), or beta-blockers (including propranolol). In patients who are elderly, volume-depleted (including those on diuretic therapy), or have renal impairment, coadministration of an NSAID with ACE inhibitors or ARBs may result in deterioration of renal function, including possible acute renal failure. These effects are usually reversible. Intervention: During concomitant use of flurbiprofen and ACE-inhibitors, ARBs, or beta-blockers, monitor blood pressure to ensure that the desired blood pressure is obtained. During concomitant use of flurbiprofen and ACE-inhibitors or ARBs in patients who are elderly, volume-depleted, or have impaired renal function, monitor for signs of worsening renal function [ see Warnings and Precautions (5. 6) When drugs are administered concomitantly, patients should be adequately hydrated. Assess renal function at the beginning of the concomitant treatment and periodically thereafter. Diuretics: Table1: Clinically significant Drug interactions with Flubriprofen Clinical Impact: Clinical studies, as well as post-marketing observations, showed that NSAIDs reduced the natriuretic effect of loop diuretics (e. , furosemide) and thiazide diuretics in some patients. This effect has been attributed to the NSAID inhibition of renal prostaglandin synthesis. Intervention: During concomitant use of flurbiprofen with diuretics, observe patients for signs of worsening renal function, in addition to assuring diuretic efficacy including antihypertensive effects [ see Warnings and Precautions (5) Digoxin Clinical Impact: The concomitant use of flurbiprofen with digoxin has been reported to increase the serum concentration and prolong the half-life of digoxin [ see Clinical Pharmacology (12. 3) Intervention: During concomitant use of flurbiprofen and digoxin, monitor serum digoxin levels. Lithium Clinical Impact: NSAIDs have produced elevations in plasma lithium levels and reductions in renal lithium clearance. The mean minimum lithium concentration increased 15%, and the renal clearance decreased by approximately 20%. This effect has been attributed to NSAID inhibition of renal prostaglandin synthesis. Intervention: During concomitant use of flurbiprofen and lithium, monitor patients for signs of lithium toxicity. Methotrexate Clinical Impact: Concomitant use of NSAIDs and methotrexate may increase the risk for methotrexate toxicity (e. , neutropenia, thrombocytopenia, renal dysfunction). Intervention: During concomitant use of flurbiprofen and methotrexate, monitor patients for methotrexate toxicity. Cyclosporine Clinical Impact: Concomitant use of flurbiprofen and cyclosporine may increase cyclosporine's nephrotoxicity. Intervention: During concomitant use of flurbiprofen and cyclosporine, monitor patients for signs of worsening renal function. NSAIDs and Salicylates Clinical Impact: Concomitant use of flurbiprofen with other NSAIDs or salicylates (e. , diflunisal, salsalate) increases the risk of GI toxicity, with little or no increase in efficacy [ see Warnings and Precautions (5. 2) Intervention: The concomitant use of flurbiprofen with other NSAIDs or salicylates is not recommended. Pemetrexed Clinical Impact: Concomitant use of flurbiprofen and pemetrexed may increase the risk of pemetrexed-associated myelosuppression, renal, and GI toxicity (see the pemetrexed prescribing information). Intervention: During concomitant use of flurbiprofen and pemetrexed, in patients with renal impairment whose creatinine clearance ranges from 45 to 79 mL/min, monitor for myelosuppression, renal and GI toxicity. Corticosteroids Clinical Impact: Concomitant use of corticosteroids with flurbiprofen may increase the risk of GI ulceration or bleeding. Intervention: Monitor patients with concomitant use of flurbiprofen with corticosteroids for signs of bleeding [ see Warnings and Precautions (5. 2) Drugs that Interfere with Hemostasis (e. warfarin, aspirin, SSRIs/SNRIs) 7 ACE Inhibitors, Angiotensin Receptor Blockers (ARB), or Beta-Blockers 7 ACE Inhibitors and ARBs 7 Diuretics 7.

OVERDOSAGE
Symptoms following acute NSAID overdosages have been typically limited to lethargy, drowsiness, nausea, vomiting, and epigastric pain, which are generally reversible with supportive care. Gastrointestinal bleeding has occurred. Hypertension, acute renal failure, respiratory depression and coma have occurred, but were rare [ see Warnings and Precautions (5.1 5.2 5.4 5.6) Manage patients with symptomatic and supportive care following an NSAID overdosage. There are no specific antidotes. Consider emesis and/or activated charcoal (60 to 100 grams in adults, 1 to 2 grams per kg of body weight in pediatric patients) and/or osmotic cathartic in symptomatic patients seen within four hours of ingestion or in patients with a large overdosage (5 to 10 times the recommended dosage). Forced diuresis, alkalinization of urine, hemodialysis, or hemoperfusion may not be useful due to high protein binding. For additional information about overdosage treatment contact a poison control center (1-800-222-1222).
NONCLINICAL TOXICOLOGY
Carcinogenesis Flurbiprofen was not carcinogenic in long-term studies in Fischer-344 and CD rats at doses up to 5 mg/kg/day and in CFLP mice at doses up to 12 mg/kg/day (0. 16-times and 0. 19-times, respectively, the human dose of 300 mg/day on a mg/m 2 Mutagenesis Flurbiprofen was not genotoxic in an in vivo micronucleus assay in rats. Impairment of Fertility No effect on male or female fertility in rats was observed after oral administration of 3 mg/kg flurbiprofen for 65 days prior to mating in males and 14 days prior to mating through Gestation Day 16 in females (equivalent to 0. 1-times the human dose of 300 mg/day on a mg/m 2.

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LURBIPR- flurbiprofen_tablet Product manual source documgent