SILICEA cause clinical trials are conducted under widely varying conditions, the adverse reactions rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. During the premarketing development of varenicline, over 4500 subjects were exposed to varenicline, with over 450 treated for at least 24 weeks and approximately 100 for a year. Most study participants were treated for 12 weeks or less. The most common adverse event associated with varenicline treatment is nausea, occurring in 30% of patients treated at the recommended dose, compared with 10% in patients taking a comparable placebo regimen [see Warnings and Precautions (5.9) ] . Table 1 shows the adverse events for varenicline and placebo in the 12- week fixed dose premarketing studies with titration in the first week [Studies 2 (titrated arm only), 4, and 5]. Adverse events were categorized using the Medical Dictionary for Regulatory Activities (MedDRA, Version 7.1). MedDRA High Level Group Terms (HLGT) reported in ≥5% of patients in the varenicline 1 mg twice daily dose group, and more commonly than in the p ionary for Regulatory Activities (MedDRA, Version 7.1). MedDRA High Level Group Terms (HLGT) reported in ≥5% of patients in the varenicline 1 mg twice daily dose group, and more commonly than in the placebo group, are listed, along with subordinate Preferred Terms (PT) reported in ≥1% of varenicline patients (and at least 0.5% more frequent than placebo). Closely related Preferred Terms such as ‘Insomnia’, ‘Initial insomnia’, ‘Middle insomnia’, ‘Early morning awakening’ were grouped, but individual patients reporting two or more grouped events are only counted once. Table 1. Common Treatment Emergent AEs (%) in the Fixed-Dose, Placebo-Controlled Studies (HLGTs >5% of Patients in the 1 mg BID varenicline Group and More Commonly than Placebo and PT ≥1% in the 1 mg BID varenicline Group, and 1 mg BID varenicline at Least 0.5% More than Placebo) SYSTEM ORGAN CLASS High Level Group Term Preferred Term Varenicline 0.5 mg BID N=129 Varenicline 1 mg BID N=821 Placebo N=805 * Includes PTs Abdominal (pain, pain upper, pain lower, discomfort, tenderness, distension) and Stomach discomfort ** Includes PTs Insomnia/Initial insomnia/Middle insomnia/Early morning awakening GASTROINTESTINAL (GI) G inal (pain, pain upper, pain lower, discomfort, tenderness, distension) and Stomach discomfort ** Includes PTs Insomnia/Initial insomnia/Middle insomnia/Early morning awakening GASTROINTESTINAL (GI) GI Signs and Symptoms Nausea 16 30 10 Abdominal Pain * 5 7 5 Flatulence 9 6 3 Dyspepsia 5 5 3 Vomiting 1 5 2 GI Motility/Defecation Conditions Constipation 5 8 3 Gastroesophageal reflux disease 1 1 0 Salivary Gland Conditions Dry mouth 4 6 4 PSYCHIATRIC DISORDERS Sleep Disorder/Disturbances Insomnia ** 19 18 13 Abnormal dreams 9 13 5 Sleep disorder 2 5 3 Nightmare 2 1 0 NERVOUS SYSTEM Headaches Headache 19 15 13 Neurological Disorders NEC Dysgeusia 8 5 4 Somnolence 3 3 2 Lethargy 2 1 0 GENERAL DISORDERS General Disorders NEC Fatigue/Malaise/Asthenia 4 7 6 RESPIR/THORACIC/MEDIAST Respiratory Disorders NEC Rhinorrhea 0 1 0 Dyspnea 2 1 1 Upper Respiratory Tract Disorder 7 5 4 SKIN/SUBCUTANEOUS TISSUE Epidermal and Dermal Conditions Rash 1 3 2 Pruritis 0 1 1 METABOLISM and NUTRITION Appetite/General Nutrition Disorders Increased appetite 4 3 2 Decreased appetite/ Anorexia 1 2 1 The overall pattern and frequency of adverse events during the longer-term premarketing trials was similar to thos neral Nutrition Disorders Increased appetite 4 3 2 Decreased appetite/ Anorexia 1 2 1 The overall pattern and frequency of adverse events during the longer-term premarketing trials was similar to those described in Table 1, though several of the most common events were reported by a greater proportion of patients with long-term use (e.g., nausea was reported in 40% of patients treated with varenicline 1 mg twice daily in a one year study, compared to 8% of placebo-treated patients). Following is a list of treatment-emergent adverse events reported by patients treated with varenicline during all premarketing clinical trials and updated based on pooled data from 18 placebo-controlled pre- and postmarketing studies, including approximately 5,000 patients treated with varenicline. Adverse events were categorized using MedDRA, Version 16.0. The listing does not include those events already listed in the previous tables or elsewhere in labeling, those events for which a drug cause was remote, those events which were so general as to be uninformative, and those events reported only once which did not have a substantial probability of being acutely life-threatening. Blood and Lymphatic Sys , those events which were so general as to be uninformative, and those events reported only once which did not have a substantial probability of being acutely life-threatening. Blood and Lymphatic System Disorders. Infrequent: anemia, lymphadenopathy. Rare: leukocytosis, splenomegaly, thrombocytopenia. Cardiac Disorders. Infrequent: angina pectoris, myocardial infarction, palpitations, tachycardia. Rare: acute coronary syndrome, arrhythmia, atrial fibrillation, bradycardia, cardiac flutter, cor pulmonale, coronary artery disease, ventricular extrasystoles. Ear and Labyrinth Disorders. Infrequent: tinnitus, vertigo. Rare: deafness, Meniere’s disease. Endocrine Disorders. Infrequent: thyroid gland disorders. Eye Disorders. Infrequent: conjunctivitis, eye irritation, eye pain, vision blurred, visual impairment. Rare: blindness transient, cataract subcapsular, dry eye, night blindness, ocular vascular disorder, photophobia, vitreous floaters. Gastrointestinal Disorders. Frequent: diarrhea, toothache. Infrequent: dysphagia, eructation, gastritis, gastrointestinal hemorrhage, mouth ulceration. Rare: enterocolitis, esophagitis, gastric ulcer, intestinal obstruction, pancreatitis acute. Ge toothache. Infrequent: dysphagia, eructation, gastritis, gastrointestinal hemorrhage, mouth ulceration. Rare: enterocolitis, esophagitis, gastric ulcer, intestinal obstruction, pancreatitis acute. General Disorders and Administration Site Conditions. Frequent: chest pain. Infrequent: chest discomfort, chills, edema, influenza-like illness, pyrexia. Hepatobiliary Disorders. Rare: gall bladder disorder. Investigations. Frequent: liver function test abnormal, weight increased. Infrequent: electrocardiogram abnormal. Rare: muscle enzyme increased, urine analysis abnormal. Metabolism and Nutrition Disorders. Infrequent: diabetes mellitus, hypoglycemia. Rare: hyperlipidemia, hypokalemia. Musculoskeletal and Connective Tissue Disorders. Frequent: arthralgia, back pain, myalgia. Infrequent: arthritis, muscle cramp, musculoskeletal pain. Rare: myositis, osteoporosis. Nervous System Disorders. Frequent: disturbance in attention, dizziness. Infrequent: amnesia, convulsion, migraine, parosmia, syncope, tremor. Rare: balance disorder, cerebrovascular accident, dysarthria, mental impairment, multiple sclerosis, VII th nerve paralysis, nystagmus, psychomotor hyperactivity, psychomotor skills imp ncope, tremor. Rare: balance disorder, cerebrovascular accident, dysarthria, mental impairment, multiple sclerosis, VII th nerve paralysis, nystagmus, psychomotor hyperactivity, psychomotor skills impaired, restless legs syndrome, sensory disturbance, transient ischemic attack, visual field defect. Psychiatric Disorders. Infrequent: dissociation, libido decreased, mood swings, thinking abnormal. Rare: bradyphrenia, disorientation, euphoric mood. Renal and Urinary Disorders. Infrequent: nocturia, pollakiuria, urine abnormality. Rare: nephrolithiasis, polyuria, renal failure acute, urethral syndrome, urinary retention. Reproductive System and Breast Disorders. Frequent : menstrual disorder. Infrequent: erectile dysfunction. Rare: sexual dysfunction. Respiratory, Thoracic and Mediastinal Disorders. Frequent: respiratory disorders. Infrequent: asthma, epistaxis, rhinitis allergic, upper respiratory tract inflammation. Rare: pleurisy, pulmonary embolism. Skin and Subcutaneous Tissue Disorders. Infrequent: acne, dry skin, eczema, erythema, hyperhidrosis, urticaria. Rare: photosensitivity reaction, psoriasis. Vascular Disorders. Infrequent: hot flush. Rare: thrombosis. Varenicline has als rs. Infrequent: acne, dry skin, eczema, erythema, hyperhidrosis, urticaria. Rare: photosensitivity reaction, psoriasis. Vascular Disorders. Infrequent: hot flush. Rare: thrombosis. Varenicline has also been studied in postmarketing trials including (1) a trial conducted in patients with chronic obstructive pulmonary disease (COPD), (2) a trial conducted in generally healthy patients (similar to those in the premarketing studies) in which they were allowed to select a quit date between days 8 and 35 of treatment (“alternative quit date instruction trial”), (3) a trial conducted in patients who did not succeed in stopping smoking during prior varenicline therapy, or who relapsed after treatment (“re-treatment trial”), (4) a trial conducted in patients with stable cardiovascular disease, (5) a trial conducted in patients with stable schizophrenia or schizoaffective disorder, (6) a trial conducted in patients with major depressive disorder, (7) a postmarketing neuropsychiatric safety outcome trial in patients without or with a history of psychiatric disorder, (8) a non-treatment extension of the postmarketing neuropsychiatric safety outcome trial that assessed CV safety, (9) a trial in me trial in patients without or with a history of psychiatric disorder, (8) a non-treatment extension of the postmarketing neuropsychiatric safety outcome trial that assessed CV safety, (9) a trial in patients who were not able or willing to quit abruptly and who were instructed to quit gradually (“gradual approach to quitting smoking trial”). Adverse events in the trial of patients with COPD (1), in the alternative quit date instruction trial (2), and in the gradual approach to quitting smoking trial (9) were similar to those observed in premarketing studies. In the re-treatment trial (3), the profile of common adverse events was similar to that previously reported, but, in addition, varenicline-treated patients also commonly reported diarrhea (6% vs. 4% in placebo-treated patients), depressed mood disorders and disturbances (6% vs. 1%), and other mood disorders and disturbances (5% vs. 2%). In the trial of patients with stable cardiovascular disease (4), more types and a greater number of cardiovascular events were reported compared to premarketing studies, as shown in Table 1 and in Table 2 below. Table 2. Cardiovascular Mortality and Nonfatal Cardiovascular Events (%) with a Fr er of cardiovascular events were reported compared to premarketing studies, as shown in Table 1 and in Table 2 below. Table 2. Cardiovascular Mortality and Nonfatal Cardiovascular Events (%) with a Frequency >1% in Either Treatment Group in the Trial of Patients with Stable Cardiovascular Disease Varenicline 1 mg BID N=353 Placebo N=350 *some procedures were part of management of nonfatal MI and hospitalization for angina Adverse Events ≥1% in either treatment group Up to 30 days after treatment Angina pectoris 3.7 2.0 Chest pain 2.5 2.3 Peripheral edema 2.0 1.1 Hypertension 1.4 2.6 Palpitations 0.6 1.1 Adjudicated Cardiovascular Mortality (up to 52 weeks) 0.3 0.6 Adjudicated Nonfatal Serious Cardiovascular Events ≥1% in either treatment group Up to 30 days after treatment Nonfatal MI 1.1 0.3 Hospitalization for angina pectoris 0.6 1.1 Beyond 30 days after treatment and up to 52 weeks Need for coronary revascularization * 2.0 0.6 Hospitalization for angina pectoris 1.7 1.1 New diagnosis of peripheral vascular disease (PVD) or admission for a PVD procedure 1.4 0.6 In the trial of patients with stable schizophrenia or schizoaffective disorder (5), 128 smokers on antipsychotic medicat s of peripheral vascular disease (PVD) or admission for a PVD procedure 1.4 0.6 In the trial of patients with stable schizophrenia or schizoaffective disorder (5), 128 smokers on antipsychotic medication were randomized 2:1 to varenicline (1 mg twice daily) or placebo for 12 weeks with 12-week non-drug follow-up. The most common treatment emergent adverse events reported in this trial are shown in Table 3 below. Table 3. Common Treatment Emergent AEs (%) in the Trial of Patients with Stable Schizophrenia or Schizoaffective Disorder Varenicline 1 mg BID N=84 Placebo N=43 Adverse Events ≥10% in the varenicline group Nausea 24 14 Headache 11 19 Vomiting 11 9 Psychiatric Adverse Events ≥5% and at a higher rate than in the placebo group Insomnia 10 5 For the trial of patients with major depressive disorder (6), the most common treatment emergent adverse events reported are shown in Table 4 below. Additionally, in this trial, patients treated with varenicline were more likely than patients treated with placebo to report one of events related to hostility and aggression (3% vs. 1%). Table 4. Common Treatment Emergent AEs (%) in the Trial of Patients with Major Depressive Disorder Varenicl reated with placebo to report one of events related to hostility and aggression (3% vs. 1%). Table 4. Common Treatment Emergent AEs (%) in the Trial of Patients with Major Depressive Disorder Varenicline 1 mg BID N=256 Placebo N=269 Adverse Events ≥10% in either treatment group Nausea 27 10 Headache 17 11 Abnormal dreams 11 8 Insomnia 11 5 Irritability 11 8 Psychiatric Adverse Events ≥2% in any treatment group and not included above Depressed mood disorders and disturbances 11 9 Anxiety 7 9 Agitation 7 4 Tension 4 3 Hostility 2 0.4 Restlessness 2 2 In the trial of patients without or with a history of psychiatric disorder (7), the most common adverse events in subjects treated with varenicline were similar to those observed in premarketing studies. Most common treatment-emergent adverse events reported in this trial are shown in Table 5 below. Table 5. Treatment Emergent Common AEs (%) in the Trial of Patients without or with a History of Psychiatric Disorder Varenicline 1 mg BID Placebo Adverse Events ≥10% in the varenicline group Entire study population, N 1982 1979 Nausea 25 7 Headache 12 10 Psychiatric Adverse Events ≥2% in any treatment group Non-psychiatric cohort, N 975 982 bo Adverse Events ≥10% in the varenicline group Entire study population, N 1982 1979 Nausea 25 7 Headache 12 10 Psychiatric Adverse Events ≥2% in any treatment group Non-psychiatric cohort, N 975 982 Abnormal dreams 8 4 Agitation 3 3 Anxiety 5 6 Depressed mood 3 3 Insomnia 10 7 Irritability 3 4 Sleep disorder 3 2 Psychiatric cohort, N 1007 997 Abnormal dreams 12 5 Agitation 5 4 Anxiety 8 6 Depressed mood 5 5 Depression 5 5 Insomnia 9 7 Irritability 5 7 Nervousness 2 3 Sleep disorder 3 2 In the non-treatment extension of the postmarketing neuropsychiatric safety outcomes trial that assessed CV safety (8), the most common adverse events in subjects treated with varenicline and occurring up to 30 days after last dose of treatment were similar to those observed in premarketing studies. 6.2 Postmarketing Experience The following adverse events have been reported during post-approval use of varenicline. Because these events are reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency or establish a causal relationship to drug exposure. There have been reports of depression, mania, psychosis, hallucinations, paranoia, delusions, hom not possible to reliably estimate their frequency or establish a causal relationship to drug exposure. There have been reports of depression, mania, psychosis, hallucinations, paranoia, delusions, homicidal ideation, aggression, hostility, anxiety, and panic, as well as suicidal ideation, suicide attempt, and completed suicide in patients attempting to quit smoking while taking varenicline [see Warnings and Precautions (5.1) ] . There have been postmarketing reports of new or worsening seizures in patients treated with varenicline [see Warnings and Precautions (5.2) ]. There have been postmarketing reports of patients experiencing increased intoxicating effects of alcohol while taking varenicline. Some reported neuropsychiatric events, including unusual and sometimes aggressive behavior [see Warnings and Precautions (5.1) and (5.3) ] . There have been reports of hypersensitivity reactions, including angioedema [see Warnings and Precautions (5.7) ] . There have also been reports of serious skin reactions, including Stevens-Johnson syndrome and erythema multiforme, in patients taking varenicline [see Warnings and Precautions (5.8) ]. There have been reports of myocardial infarction ( ous skin reactions, including Stevens-Johnson syndrome and erythema multiforme, in patients taking varenicline [see Warnings and Precautions (5.8) ]. There have been reports of myocardial infarction (MI) and cerebrovascular accident (CVA) including ischemic and hemorrhagic events in patients taking varenicline. In the majority of the reported cases, patients had pre-existing cardiovascular disease and/or other risk factors. Although smoking is a risk factor for MI and CVA, based on temporal relationship between medication use and events, a contributory role of varenicline cannot be ruled out [see Warnings and Precautions (5.5) ] . There have been reports of hyperglycemia in patients following initiation of varenicline. There have been reports of somnambulism, some resulting in harmful behavior to self, others, or property in patients treated with varenicline [see Warnings and Precautions (5.6) ] . Use for the preparation of the patient's skin prior to surgery. Helps to reduce bacteria that potentially can cause skin infection. Purposes Antiseptic Antiseptic Warnings For external use only. Flammable, keep away from fire or flame. To reduce the risk of fire, PREP CAREFULLY: do not use 26-mL applicator for head and neck surgery do not use on an area smaller than 8.4 in. × 8.4 in. Use a smaller applicator instead. solution contains alcohol and gives off flammable vapors avoid getting solution into hairy areas. Hair may take up to 1 hour to dry. Wet hair is flammable. do not drape or use ignition source (e.g., cautery, laser) until solution is completely dry (minimum of 3 minutes on hairless skin; up to 1 hour in hair) do not allow solution to pool remove wet materials from prep area Allergy alert: This product may cause a severe allergic reaction. Symptoms may include: wheezing/difficulty breathing shock facial swelling hives rash If an allergic reaction occurs, stop use and seek medical help right away. Do not use on patients allergic to chlorhexidine gluconate or any other ingredient in this product for lumbar puncture or in contact with meninges on open skin wounds or as a ge dical help right away. Do not use on patients allergic to chlorhexidine gluconate or any other ingredient in this product for lumbar puncture or in contact with meninges on open skin wounds or as a general skin cleanser When using this product keep out of eyes, ears, and mouth. May cause serious or permanent injury if permitted to enter and remain. If contact occurs, rinse with cold water right away and contact a doctor. Stop use and ask a doctor if irritation, sensitization, or allergic reaction occurs. These may be signs of a serious condition. Keep out of reach of children. If swallowed, get medical help or contact a Poison Control Center right away. Allergy alert: This product may cause a severe allergic reaction. Symptoms may include: wheezing/difficulty breathing shock facial swelling hives rash If an allergic reaction occurs, stop use and seek medical help right away. Directions use with care in premature infants or infants under 2 months of age. These products may cause irritation or chemical burns. use in a well ventilated area maximal treatment area for one applicator is approximately 13.2 in. × 13.2 in. (1126 cm 2). Do not use 26-ml applicator for area smaller than 8.4 i ion or chemical burns. use in a well ventilated area maximal treatment area for one applicator is approximately 13.2 in. × 13.2 in. (1126 cm 2). Do not use 26-ml applicator for area smaller than 8.4 in. x 8.4 in. Use a smaller applicator instead. Do not use 26-ml applicator for head and neck surgery remove applicator from package; do not touch sponge hold the applicator with the sponge down. Pinch wing only once to activate the ampules and release the antiseptic. wet the sponge by pressing and releasing the sponge against the treatment area until liquid is visible on the skin completely wet the treatment area with antiseptic dry surgical sites (e.g., abdomen or arm): use gentle repeated back-and-forth strokes for 30 seconds moist surgical sites (e.g., inguinal fold): use gentle repeated back-and-forth strokes for 2 minutes do not allow solution to pool; tuck prep towels to absorb solution, and then remove allow the solution to completely dry (minimum of 3 minutes on hairless skin; up to 1 hour in hair). Do not blot or wipe away. discard the applicator after a single use along with any portion of the solution not required to cover the prep area. It is not necessary to use the entire o 1 hour in hair). Do not blot or wipe away. discard the applicator after a single use along with any portion of the solution not required to cover the prep area. It is not necessary to use the entire amount available. Stop use and ask a doctor if irritation, sensitization, or allergic reaction occurs. These may be signs of a serious condition. Keep out of reach of children. If swallowed, get medical help or contact a Poison Control Center right away. Uses • temporarily relieves minor aches and pains due to: • minor pain of arthritis • muscular aches • backache • menstrual cramps • headache • toothache • the common cold • temporarily reduces fever Purpose Pain reliever/fever reducer Warnings Allergy alert: Naproxen sodium may cause a severe allergic reaction, especially in people allergic to aspirin. Symptoms may include: • hives • facial swelling • asthma (wheezing) • shock • skin reddening • rash • blisters If an allergic reaction occurs, stop use and seek medical help right away. Stomach bleeding warning: This product contains an NSAID, which may cause severe stomach bleeding. The chance is higher if you: • are age 60 or older • have had stomach ulcers or bleeding problems • take a blood thinning (anticoagulant) or steroid drug • take other drugs containing prescription or nonprescription NSAIDs (aspirin, ibuprofen, naproxen, or others) • have 3 or more alcoholic drinks every day while using this product • take more or for a longer time than directed Do not use • if you have ever had an allergic reaction to any other pain reliever/fever reducer • right before or after heart surgery Ask a doctor before use if • the stomach ble er time than directed Do not use • if you have ever had an allergic reaction to any other pain reliever/fever reducer • right before or after heart surgery Ask a doctor before use if • the stomach bleeding warning applies to you • you have a history of stomach problems, such as heartburn • you have high blood pressure, heart disease, liver cirrhosis, or kidney disease • you are taking a diuretic • you have problems or serious side effects from taking pain relievers or fever reducers • you have asthma Ask a doctor or pharmacist before use if you are • under a doctor’s care for any serious condition • taking any other drug When using this product • take with food or milk if stomach upset occurs • the risk of heart attack or stroke may increase if you use more than directed or for longer than directed Stop use and ask a doctor if • you experience any of the following signs of stomach bleeding: • feel faint • vomit blood • have bloody or black stools • have stomach pain that does not get better • pain gets worse or lasts more than 10 days • fever gets worse or lasts more than 3 days • redness or swelling is present in the painful area • any new symptoms appear • you have difficulty swa etter • pain gets worse or lasts more than 10 days • fever gets worse or lasts more than 3 days • redness or swelling is present in the painful area • any new symptoms appear • you have difficulty swallowing • it feels like the capsule is stuck in your throat If pregnant or breast-feeding, ask a health professional before use. It is especially important not to use naproxen sodium during the last 3 months of pregnancy unless definitely directed to do so by a doctor because it may cause problems in the unborn child or complications during delivery. Keep out of reach of children. In case of overdose, get medical help or contact a Poison Control Center right away. (1-800-222-1222) Directions • do not take more than directed • the smallest effective dose should be used • drink a full glass of water with each dose • if taken with food, this product may take longer to work adults and children 12 years and older: • take 1 capsule every 8 to 12 hours while symptoms last • for the first dose you may take 2 capsules within the first hour • do not exceed 2 capsules in any 8- to 12-hour period • do not exceed 3 capsules in a 24-hour period children under 12 years: • ask a doctor Ask a doctor be may take 2 capsules within the first hour • do not exceed 2 capsules in any 8- to 12-hour period • do not exceed 3 capsules in a 24-hour period children under 12 years: • ask a doctor Ask a doctor before use if • the stomach bleeding warning applies to you • you have a history of stomach problems, such as heartburn • you have high blood pressure, heart disease, liver cirrhosis, or kidney disease • you are taking a diuretic • you have problems or serious side effects from taking pain relievers or fever reducers • you have asthma Stop use and ask a doctor if • you experience any of the following signs of stomach bleeding: • feel faint • vomit blood • have bloody or black stools • have stomach pain that does not get better • pain gets worse or lasts more than 10 days • fever gets worse or lasts more than 3 days • redness or swelling is present in the painful area • any new symptoms appear • you have difficulty swallowing • it feels like the capsule is stuck in your throat Keep out of reach of children. In case of overdose, get medical help or contact a Poison Control Center right away. (1-800-222-1222) Use for relief of occasional sleeplessness caused by stress and repetitive thoughts Active ingredients Each 5X (HPUS) Purpose White Chestnut (Aesculus hippocastanum) Relief from repetitive thoughts Rock Rose (Helianthemum nummularium) Courage and presence of mind Clematis (Clematis vitalba) Focus when ungrounded Impatiens (Impatiens glandulifera) Patience with problems and people Cherry Plum (Prunus cerasifera) Balanced mind when losing control Star of Bethlehem (Ornithogalum umbellatum) Softens impact of shock Warnings When using this product keep away from eyes Stop use and ask a doctor if sleeplessness persists for more than two weeks: insomnia can be a symptom of serious underlying medical illness If pregnant or breastfeeding, ask a health professional before use. Keep out of reach of children. In case of overdose, get medical help or contact a Poison Control Center right away. Directions adults: apply 2 sprays onto the tongue. Additional sprays may be taken during the night as needed. children under 12: ask a doctor Stop use and ask a doctor if sleeplessness persists for more than two weeks: insomnia can be a symptom of serious underlying medical illness Keep out of reach of c ded. children under 12: ask a doctor Stop use and ask a doctor if sleeplessness persists for more than two weeks: insomnia can be a symptom of serious underlying medical illness Keep out of reach of children. In case of overdose, get medical help or contact a Poison Control Center right away. Uses temporarily relieves minor aches and pains due to: headache the common cold backache minor pain of arthritis toothache muscular aches premenstrual and menstrual cramps temporarily reduces fever Purpose Pain reliever/fever reducer Warnings Liver warning: This product contains acetaminophen. Severe liver damage may occur if you take more than 4,000 mg of acetaminophen in 24 hours with other drugs containing acetaminophen 3 or more alcoholic drinks every day while using this product Allergy alert: Acetaminophen may cause severe skin reactions. Symptoms may include: skin reddening blisters rash If a skin reaction occurs, stop use and seek medical help right away. Do not use if you are allergic to acetaminophen or any of the inactive ingredients in this product with any other drug containing acetaminophen (prescription or nonprescription). If you are not sure whether a drug contains acetaminophen, ask a doctor or pharmacist. Ask a doctor before use if you have liver disease. Ask a doctor or pharmacist before use if you are taking the blood thinning drug warfarin. Stop use and ask a doctor if new symptoms occur pain gets worse or lasts more than 10 days fever gets worse or lasts mor or or pharmacist before use if you are taking the blood thinning drug warfarin. Stop use and ask a doctor if new symptoms occur pain gets worse or lasts more than 10 days fever gets worse or lasts more than 3 days redness or swelling is present These could be signs of a serious condition. If pregnant or breast-feeding, ask a health professional before use. Keep out of reach of children. In case of overdose, get medical help or contact a Poison Control Center right away. Prompt medical attention is critical for adults as well as for children even if you do not notice any signs or symptoms. Directions do not take more than directed adults and children 12 years and over take 2 gelcaps every 6 hours while symptoms last do not take more than 6 gelcaps in 24 hours, unless directed by a doctor do not take for more than 10 days unless directed by a doctor children under 12 years: ask a doctor Ask a doctor before use if you have liver disease. Stop use and ask a doctor if new symptoms occur pain gets worse or lasts more than 10 days fever gets worse or lasts more than 3 days redness or swelling is present These could be signs of a serious condition. Keep out of reach of children. In case of n gets worse or lasts more than 10 days fever gets worse or lasts more than 3 days redness or swelling is present These could be signs of a serious condition. Keep out of reach of children. In case of overdose, get medical help or contact a Poison Control Center right away. Prompt medical attention is critical for adults as well as for children even if you do not notice any signs or symptoms. Uses • helps prevent sunburn • higher SPF gives more sunburn protection PURPOSE Sunscreen Directions • apply evenly each morning before sun exposure • do not use on infants under 6 months • reapply as needed Keep out of the reach of children. If swallowed, get medical help or contact a Poison Control Center right away Uses temporarily relieves the minor aches and pains of muscles and joints associated with • simple backache • arthritis • strains • bruises • sprains Purpose Topical analgesic Warnings For external use only Do not use other than as directed When using this product • avoid contact with the eyes or mucous membranes • do not apply to wounds or damaged skin • do not bandage tightly • do not use with a heating pad Stop use and ask a doctor if • condition worsens or symptoms persist for more than 7 days • symptoms clear up and occur again within a few days • redness is present or excessive skin irritation develops Keep out of reach of children. If swallowed, get medical help or contact a Poison Control Center right away. (1-800-222-1222) Directions • use only as directed • adults & children 12 years of age and older: apply to affected area not more than 3 to 4 times daily • children under 12 years of age: ask a doctor Stop use and ask a doctor if • condition worsens or symptoms persist for more than 7 days • symptoms clear up and occur again within a few days • redness is present or excessive skin irritation develops Keep out of reach of children. If swallowed, get medical help or contac ore than 7 days • symptoms clear up and occur again within a few days • redness is present or excessive skin irritation develops Keep out of reach of children. If swallowed, get medical help or contact a Poison Control Center right away. (1-800-222-1222) 1 INDICATIONS AND USAGE Plavix is a P2Y 12 platelet inhibitor indicated for: Acute coronary syndrome Recent myocardial infarction (MI), recent stroke, or established peripheral arterial disease. Plavix has been shown to reduce the combined endpoint of new ischemic stroke (fatal or not), new MI (fatal or not), and other vascular death. ( 1.2 ) 1.1 Acute Coronary Syndrome (ACS) For patients with non-ST-segment elevation ACS [unstable angina (UA)/non-ST-elevation myocardial infarction (NSTEMI)], including patients who are to be managed medically and those who are to be managed with coronary revascularization, Plavix has been shown to decrease the rate of a combined endpoint of cardiovascular death, myocardial infarction (MI), or stroke as well as the rate of a combined endpoint of cardiovascular death, MI, stroke, or refractory ischemia. For patients with ST-elevation myocardial infarction (STEMI), Plavix has been shown to reduce the rate of death from any cause and the rate of a combined endpoint of death, re-infarction, or stroke. The benefit for patients who undergo primary percutaneous coronary intervention is unknown. The optimal duration of Plavix therapy in ACS is unknown. 1.2 endpoint of death, re-infarction, or stroke. The benefit for patients who undergo primary percutaneous coronary intervention is unknown. The optimal duration of Plavix therapy in ACS is unknown. 1.2 Recent MI, Recent Stroke, or Established Peripheral Arterial Disease For patients with a history of recent myocardial infarction (MI), recent stroke, or established peripheral arterial disease, Plavix has been shown to reduce the rate of a combined endpoint of new ischemic stroke (fatal or not), new MI (fatal or not), and other vascular death. 2 DOSAGE AND ADMINISTRATION Acute coronary syndrome ( 2.1 ) Recent MI, recent stroke, or established peripheral arterial disease: 75 mg once daily ( 2.2 ) 2.1 Acute Coronary Syndrome Plavix can be administered with or without food [see Clinical Pharmacology (12.3) ] For patients with non-ST-elevation ACS (UA/NSTEMI), initiate Plavix with a single 300 mg oral loading dose and then continue at 75 mg once daily. Initiate aspirin (75–325 mg once daily) and continue in combination with Plavix [see Clinical Studies (14.1) ] . For patients with STEMI, the recommended dose of Plavix is 75 mg once daily orally, administered in combination with aspirin (75 nd continue in combination with Plavix [see Clinical Studies (14.1) ] . For patients with STEMI, the recommended dose of Plavix is 75 mg once daily orally, administered in combination with aspirin (75–325 mg once daily), with or without thrombolytics. Plavix may be initiated with or without a loading dose [see Clinical Studies (14.1) ] . 2.2 Recent MI, Recent Stroke, or Established Peripheral Arterial Disease The recommended daily dose of Plavix is 75 mg once daily orally, with or without food [see Clinical Pharmacology (12.3) ] . 2.3 CYP2C19 Poor Metabolizers CYP2C19 poor metabolizer status is associated with diminished antiplatelet response to clopidogrel. Although a higher dose regimen (600 mg loading dose followed by 150 mg once daily) in poor metabolizers increases antiplatelet response [see Clinical Pharmacology (12.5) ] , an appropriate dose regimen for this patient population has not been established in clinical outcome trials. 6 ADVERSE REACTIONS The following serious adverse reactions are discussed below and elsewhere in the labeling: Bleeding [see Warnings and Precautions (5.2) ] Thrombotic thrombocytopenic purpura [see Warnings and Precautions (5.5) ] Bleeding, includin reactions are discussed below and elsewhere in the labeling: Bleeding [see Warnings and Precautions (5.2) ] Thrombotic thrombocytopenic purpura [see Warnings and Precautions (5.5) ] Bleeding, including life-threatening and fatal bleeding, is the most commonly reported adverse reaction. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Bristol-Myers Squibb/Sanofi Pharmaceuticals Partnership at 1-800-633-1610 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Studies Experience Because clinical trials are conducted under widely varying conditions and durations of follow up, 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. Plavix has been evaluated for safety in more than 54,000 patients, including over 21,000 patients treated for 1 year or more. The clinically important adverse reactions observed in trials comparing Plavix plus aspirin to placebo plus aspirin and trials comparing Plavix alone to aspirin alone are discussed below. Bleeding CURE In CURE, Plavix use with aspirin was associated with an increase in major bleeding spirin to placebo plus aspirin and trials comparing Plavix alone to aspirin alone are discussed below. Bleeding CURE In CURE, Plavix use with aspirin was associated with an increase in major bleeding (primarily gastrointestinal and at puncture sites) compared to placebo with aspirin (see Table 1). The incidence of intracranial hemorrhage (0.1%) and fatal bleeding (0.2%) were the same in both groups. Other bleeding events that were reported more frequently in the clopidogrel group were epistaxis, hematuria, and bruise. The overall incidence of bleeding is described in Table 1. Table 1: CURE Incidence of Bleeding Complications (% patients) Event Plavix (+ aspirin) Other standard therapies were used as appropriate. Placebo (+ aspirin) p-value (n=6259) (n=6303) Major bleeding Life-threatening and other major bleeding. 3.7 Major bleeding event rate for Plavix + aspirin was dose-dependent on aspirin: <100 mg = 2.6%; 100–200 mg = 3.5%; >200 mg = 4.9% Major bleeding event rates for Plavix + aspirin by age were: <65 years = 2.5%, ≥65 to <75 years = 4.1%, ≥75 years = 5.9% 2.7 Major bleeding event rate for placebo + aspirin was dose-dependent on aspirin: <100 mg = 2.0%; 100–200 mg = 2.3%; >20 pirin by age were: <65 years = 2.5%, ≥65 to <75 years = 4.1%, ≥75 years = 5.9% 2.7 Major bleeding event rate for placebo + aspirin was dose-dependent on aspirin: <100 mg = 2.0%; 100–200 mg = 2.3%; >200 mg = 4.0% Major bleeding event rates for placebo + aspirin by age were: <65 years = 2.1%, ≥65 to <75 years = 3.1%, ≥75 years = 3.6% 0.001 Life-threatening bleeding 2.2 1.8 0.13 Fatal 0.2 0.2 5 g/dL hemoglobin drop 0.9 0.9 Requiring surgical intervention 0.7 0.7 Hemorrhagic strokes 0.1 0.1 Requiring inotropes 0.5 0.5 Requiring transfusion (≥4 units) 1.2 1.0 Other major bleeding 1.6 1.0 0.005 Significantly disabling 0.4 0.3 Intraocular bleeding with significant loss of vision 0.05 0.03 Requiring 2–3 units of blood 1.3 0.9 Minor bleeding Led to interruption of study medication. 5.1 2.4 < 0.001 Ninety-two percent (92%) of the patients in the CURE study received heparin or low molecular weight heparin (LMWH), and the rate of bleeding in these patients was similar to the overall results. COMMIT In COMMIT, similar rates of major bleeding were observed in the Plavix and placebo groups, both of which also received aspirin (see Table 2). Table 2: Incidence of Bleeding Events in COMMIT (% patie T In COMMIT, similar rates of major bleeding were observed in the Plavix and placebo groups, both of which also received aspirin (see Table 2). Table 2: Incidence of Bleeding Events in COMMIT (% patients) Type of bleeding Plavix (+ aspirin) (n=22961) Placebo (+ aspirin) (n=22891) p-value Major Major bleeds were cerebral bleeds or non-cerebral bleeds thought to have caused death or that required transfusion. noncerebral or cerebral bleeding The relative rate of major noncerebral or cerebral bleeding was independent of age. Event rates for Plavix + aspirin by age were: <60 years = 0.3%, ≥60 to <70 years = 0.7%, ≥70 years = 0.8%. Event rates for placebo + aspirin by age were: <60 years = 0.4%, ≥60 to <70 years = 0.6%, ≥70 years = 0.7%. 0.6 0.5 0.59 Major noncerebral 0.4 0.3 0.48 Fatal 0.2 0.2 0.90 Hemorrhagic stroke 0.2 0.2 0.91 Fatal 0.2 0.2 0.81 Other noncerebral bleeding (non-major) 3.6 3.1 0.005 Any noncerebral bleeding 3.9 3.4 0.004 CAPRIE (Plavix vs. Aspirin) In CAPRIE, gastrointestinal hemorrhage occurred at a rate of 2.0% in those taking Plavix vs. 2.7% in those taking aspirin; bleeding requiring hospitalization occurred in 0.7% and 1.1%, respectively. The incidence of intracr inal hemorrhage occurred at a rate of 2.0% in those taking Plavix vs. 2.7% in those taking aspirin; bleeding requiring hospitalization occurred in 0.7% and 1.1%, respectively. The incidence of intracranial hemorrhage was 0.4% for Plavix compared to 0.5% for aspirin. Other bleeding events that were reported more frequently in the Plavix group were epistaxis and hematoma. Other Adverse Events In CURE and CHARISMA, which compared Plavix plus aspirin to aspirin alone, there was no difference in the rate of adverse events (other than bleeding) between Plavix and placebo. In CAPRIE, which compared Plavix to aspirin, pruritus was more frequently reported in those taking Plavix. No other difference in the rate of adverse events (other than bleeding) was reported. 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of Plavix. Because these reactions are reported voluntarily from a population of an unknown size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Blood and lymphatic system disorders : Agranulocytosis, aplastic anemia/pancytopenia, thrombotic thrombocytopenic reliably estimate their frequency or establish a causal relationship to drug exposure. Blood and lymphatic system disorders : Agranulocytosis, aplastic anemia/pancytopenia, thrombotic thrombocytopenic purpura (TTP) Gastrointestinal disorders: Gastrointestinal and retroperitoneal hemorrhage with fatal outcome, colitis (including ulcerative or lymphocytic colitis), pancreatitis, stomatitis General disorders and administration site condition : Fever, hemorrhage of operative wound Hepato-biliary disorders: Acute liver failure, hepatitis (non-infectious), abnormal liver function test Immune system disorders: Hypersensitivity reactions, anaphylactoid reactions, serum sickness Musculoskeletal, connective tissue and bone disorders: Musculoskeletal bleeding, myalgia, arthralgia, arthritis Nervous system disorders : Taste disorders, fatal intracranial bleeding Eye disorders : Eye (conjunctival, ocular, retinal) bleeding Psychiatric disorders: Confusion, hallucinations Respiratory, thoracic and mediastinal disorders: Bronchospasm, interstitial pneumonitis, respiratory tract bleeding Renal and urinary disorders: Glomerulopathy, increased creatinine levels Skin and subcutaneous tissue disorders ediastinal disorders: Bronchospasm, interstitial pneumonitis, respiratory tract bleeding Renal and urinary disorders: Glomerulopathy, increased creatinine levels Skin and subcutaneous tissue disorders: Maculopapular or erythematous rash, urticaria, bullous dermatitis, eczema, toxic epidermal necrolysis, Stevens-Johnson syndrome, angioedema, erythema multiforme, skin bleeding, lichen planus Vascular disorders: Vasculitis, hypotension Uses helps loosen phlegm (mucus) and thin bronchial secretions to drain bronchial tubes temporarily relieves these symptoms occurring with a cold: nasal congestion cough due to minor throat and bronchial irritation Purposes Cough suppressant Expectorant Nasal decongestant Warnings Do not use if you are now taking a prescription monoamine oxidase inhibitor (MAOI) (certain drugs for depression, psychiatric or emotional conditions, or Parkinson’s disease), or for 2 weeks after stopping the MAOI drug. If you do not know if your prescription drug contains an MAOI, ask a doctor or pharmacist before taking this product. Ask a doctor before use if you have heart disease diabetes high blood pressure thyroid disease trouble urinating due to an enlarged prostate gland cough that occurs with too much phlegm (mucus) cough that lasts or is chronic such as occurs with smoking, asthma, chronic bronchitis or emphysema Ask a doctor or pharmacist before use if you are taking any other oral nasal decongestant or stimulant. When using this product, do not use more than directed. Stop use and ask a doctor if nervousness, dizziness, or sleeplessness occur symptoms do not get better within 7 days or are a tant or stimulant. When using this product, do not use more than directed. Stop use and ask a doctor if nervousness, dizziness, or sleeplessness occur symptoms do not get better within 7 days or are accompanied by fever cough lasts more than 7 days, comes back, or is accompanied by fever, rash, or persistent headache. These could be signs of a serious condition. If pregnant or breast-feeding, ask a health professional before use. Keep out of reach of children. In case of overdose, get medical help or contact a Poison Control Center (1800-222-122) right away. Directions do not take more than 6 doses in any 24-hour period measure only with dosing cup provided. Do not use any other dosing device. keep dosing cup with product mL = milliliter this adults product is not intended for use in children under 12 years of age adult and children 12 years and over: 10 mL every 4 hours children under 12 years : do not use Ask a doctor before use if you have heart disease diabetes high blood pressure thyroid disease trouble urinating due to an enlarged prostate gland cough that occurs with too much phlegm (mucus) cough that lasts or is chronic such as occurs with smoking, asthma, chronic bronchiti thyroid disease trouble urinating due to an enlarged prostate gland cough that occurs with too much phlegm (mucus) cough that lasts or is chronic such as occurs with smoking, asthma, chronic bronchitis or emphysema Stop use and ask a doctor if nervousness, dizziness, or sleeplessness occur symptoms do not get better within 7 days or are accompanied by fever cough lasts more than 7 days, comes back, or is accompanied by fever, rash, or persistent headache. These could be signs of a serious condition. Keep out of reach of children. In case of overdose, get medical help or contact a Poison Control Center (1800-222-122) right away. Uses For the temporary relief of burning and irritation due to dryness of the eye For the temporary relief of discomfort due to minor irritations of the eye or to exposure to wind or sun For use as a protectant against further irritation or to relieve dryness of the eye Purpose lubricant Eye Drops Warnings For external use only Do not use If solution changes color or becomes cloudy If you are sensitive to any ingredient in this product When using this product To avoid contamination do not touch tip of container to any surface Replace cap after using Stop use and ask a doctor if You experience eye pain, changes in vision, continued redness or irritation of the eye, or if the condition worsens or persists for more than 72 hours Keep out of reach of children. If swallowed, get medical help or contact a Poison Control Center right away. Directions Instill 1 or 2 drops in the affected eye(s) as needed. Stop use and ask a doctor if You experience eye pain, changes in vision, continued redness or irritation of the eye, or if the condition worsens or persists for more than 72 hours Keep out of reach of children. If swallowed, get medical help or contact a Poison Control Center right away. INDICATIONS AND USAGE: Central Diabetes Insipidus: Desmopressin acetate tablets are indicated as antidiuretic replacement therapy in the management of central diabetes insipidus and for the management of the temporary polyuria and polydipsia following head trauma or surgery in the pituitary region. Desmopressin acetate tablets are ineffective for the treatment of nephrogenic diabetes insipidus. Patients were selected for therapy based on the diagnosis by means of the water deprivation test, the hypertonic saline infusion test, and/or response to antidiuretic hormone. Continued response to desmopressin acetate can be monitored by measuring urine volume and osmolality. Primary Nocturnal Enuresis: Desmopressin acetate tablets are indicated for the management of primary nocturnal enuresis. Desmopressin acetate tablets may be used alone or as an adjunct to behavioral conditioning or other non-pharmacologic intervention. WARNINGS: Very rare cases of hyponatremia have been reported from world-wide postmarketing experience in patients treated with desmopressin acetate. Desmopressin acetate is a potent antidiuretic which, when administered, may lead to water intoxication and/or hyponatremia -wide postmarketing experience in patients treated with desmopressin acetate. Desmopressin acetate is a potent antidiuretic which, when administered, may lead to water intoxication and/or hyponatremia. Unless properly diagnosed and treated hyponatremia can be fatal. Therefore, fluid restriction is recommended and should be discussed with the patient and/or guardian. Careful medical supervision is required. When desmopressin acetate tablets are administered, in particular in pediatric and geriatric patients, fluid intake should be adjusted downward to decrease the potential occurrence of water intoxication and hyponatremia. (See PRECAUTIONS , Pediatric Use and Geriatric Use .) All patients receiving desmopressin acetate therapy should be observed for the following signs of symptoms associated with hyponatremia: headache, nausea/vomiting, decreased serum sodium, weight gain, restlessness, fatigue, lethargy, disorientation, depressed reflexes, loss of appetite, irritability, muscle weakness, muscle spasms or cramps and abnormal mental status such as hallucinations, decreased consciousness and confusion. Severe symptoms may include one or a combination of the following: seizure, coma a ss, muscle spasms or cramps and abnormal mental status such as hallucinations, decreased consciousness and confusion. Severe symptoms may include one or a combination of the following: seizure, coma and/or respiratory arrest. Particular attention should be paid to the possibility of the rare occurrence of an extreme decrease in plasma osmolality that may result in seizures which could lead to coma. Desmopressin acetate should be used with caution in patients with habitual or psychogenic polydipsia who may be more likely to drink excessive amounts of water, putting them at greater risk of hyponatremia. DOSAGE AND ADMINISTRATION: Central Diabetes Insipidus: The dosage of desmopressin acetate tablets must be determined for each individual patient and adjusted according to the diurnal pattern of response. Response should be estimated by two parameters: adequate duration of sleep and adequate, not excessive, water turnover. Patients previously on intranasal desmopressin acetate therapy should begin tablet therapy twelve hours after the last intranasal dose. During the initial dose titration period, patients should be observed closely and appropriate safety parameters measured to assure ld begin tablet therapy twelve hours after the last intranasal dose. During the initial dose titration period, patients should be observed closely and appropriate safety parameters measured to assure adequate response. Patients should be monitored at regular intervals during the course of desmopressin acetate tablets therapy to assure adequate antidiuretic response. Modifications in dosage regimen should be implemented as necessary to assure adequate water turnover. Fluid restriction should be observed. (See WARNINGS , PRECAUTIONS , Pediatric Use and Geriatric Use .) Adults and Children: It is recommended that patients be started on doses of 0.05 mg (1/2 of the 0.1 mg tablet) two times a day and individually adjusted to their optimum therapeutic dose. Most patients in clinical trials found that the optimal dosage range is 0.1 mg to 0.8 mg daily, administered in divided doses. Each dose should be separately adjusted for an adequate diurnal rhythm of water turnover. Total daily dosage should be increased or decreased in the range of 0.1 mg to 1.2 mg divided into two or three daily doses as needed to obtain adequate antidiuresis. See Pediatric Use subsection for special considerations ould be increased or decreased in the range of 0.1 mg to 1.2 mg divided into two or three daily doses as needed to obtain adequate antidiuresis. See Pediatric Use subsection for special considerations when administering desmopressin acetate to pediatric diabetes insipidus patients. Geriatric Use: This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function. (See CLINICAL PHARMACOLOGY, Human Pharmacokinetics , CONTRAINDICATIONS , and PRECAUTIONS , Geriatric Use .) Primary Nocturnal Enuresis: The dosage of desmopressin acetate tablets must be determined for each individual patient and adjusted according to response. Patients previously on intranasal desmopressin acetate therapy can begin tablet therapy the night following (24 hours after) the last intranasal dose. The recommended initial dose for patients age 6 years and older is 0.2 mg at bedtime. The dose may be titrated up to 0.6 mg to achieve the desired response. ADVE hours after) the last intranasal dose. The recommended initial dose for patients age 6 years and older is 0.2 mg at bedtime. The dose may be titrated up to 0.6 mg to achieve the desired response. ADVERSE REACTIONS: Infrequently, large doses of the intranasal formulations of desmopressin acetate and desmopressin acetate injection have produced transient headache, nausea, flushing and mild abdominal cramps. These symptoms have disappeared with reduction in dosage. Central Diabetes Insipidus: In long-term clinical studies in which patients with diabetes insipidus were followed for periods up to 44 months of desmopressin acetate tablet therapy, transient increases in AST (SGOT) no higher than 1.5 times the upper limit of normal were occasionally observed. Elevated AST (SGOT) returned to the normal range despite continued use of desmopressin acetate tablets. Primary Nocturnal Enuresis: The only adverse event occurring in ≥ 3% of patients in controlled clinical trials with desmopressin acetate tablets that was probably, possibly, or remotely related to study drug was headache (4% desmopressin acetate, 3% placebo). Other: The following adverse events have been reported; however, their rel te tablets that was probably, possibly, or remotely related to study drug was headache (4% desmopressin acetate, 3% placebo). Other: The following adverse events have been reported; however, their relationship to desmopressin acetate has not been established: abnormal thinking, diarrhea, and edema-weight gain. See WARNINGS for the possibility of water intoxication and hyponatremia. INDICATIONS AND USAGE Polymyxin B sulfate and trimethoprim ophthalmic solution is indicated in the treatment of surface ocular bacterial infections, including acute bacterial conjunctivitis, and blepharoconjunctivitis, caused by susceptible strains of the following microorganisms: Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae, Streptococcus viridans, Haemophilus influenzae and Pseudomonas aeruginosa. 1 1 Efficacy for this organism in this organ system was studied in fewer than 10 infections. WARNINGS NOT FOR INJECTION INTO THE EYE. If a sensitivity reaction to polymyxin B sulfate and trimethoprim ophthalmic solution occurs, discontinue use. Polymyxin B sulfate and trimethoprim ophthalmic solution is not indicated for the prophylaxis or treatment of ophthalmia neonatorum. DOSAGE AND ADMINISTRATION In mild to moderate infections, instill one drop in the affected eye(s) every 3 hours (maximum of 6 doses per day) for a period of 7 to 10 days. ADVERSE REACTIONS The most frequent adverse reaction to polymyxin B sulfate and trimethoprim ophthalmic solution is local irritation consisting of increased redness, burning, stinging, and/or itching. This may occur o The most frequent adverse reaction to polymyxin B sulfate and trimethoprim ophthalmic solution is local irritation consisting of increased redness, burning, stinging, and/or itching. This may occur on instillation, within 48 hours, or at any time with extended use. There are also multiple reports of hypersensitivity reactions consisting of lid edema, itching, increased redness, tearing, and/or circumocular rash. Photosensitivity has been reported in patients taking oral trimethoprim. To report SUSPECTED ADVERSE REACTIONS, contact Bausch & Lomb Incorporated at 1-800-553-5340 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . INDICATIONS AND USAGE Lorazepam is indicated for the management of anxiety disorders or for the short-term relief of the symptoms of anxiety or anxiety associated with depressive symptoms. Anxiety or tension associated with the stress of everyday life usually does not require treatment with an anxiolytic. The effectiveness of lorazepam in long-term use, that is, more than 4 months, has not been assessed by systematic clinical studies. The physician should periodically reassess the usefulness of the drug for the individual patient. WARNINGS Lorazepam is not recommended for use in patients with a primary depressive disorder of psychosis. As with all patients on CNS-acting drugs, patients receiving lorazepam should be warned not to operate dangerous machinery or motor vehicles and that their tolerance for alcohol and other CNS depressants will be diminished. DOSAGE AND ADMINISTRATION Lorazepam is administered orally. For optimal results, dose, frequency of administration, and duration of therapy should be individualized according to patient response. To facilitate this, 0.5 mg, 1 mg, and 2 mg tablets are available. The usual range is 2 to 6 mg/day given in divided doses, the largest d therapy should be individualized according to patient response. To facilitate this, 0.5 mg, 1 mg, and 2 mg tablets are available. The usual range is 2 to 6 mg/day given in divided doses, the largest dose being taken before bedtime, but the daily dosage may vary from 1 to 10 mg/day. For anxiety, most patients require an initial dose of 2 to 3 mg/day given b.i.d. or t.i.d. For insomnia due to anxiety or transient situational stress, a single daily dose of 2 to 4 mg may be given, usually at bedtime. For elderly or debilitated patients, an initial dosage of 1 to 2 mg/day in divided doses is recommended, to be adjusted as needed and tolerated. The dosage of lorazepam should be increased gradually when needed to help avoid adverse effects. When higher dosage is indicated, the evening dose should be increased before the daytime doses. ADVERSE REACTIONS Adverse reactions, if they occur, are usually observed at the beginning of therapy and generally disappear on continued medication or upon decreasing the dose. In a sample of about 3,500 anxious patients, the most frequent adverse reaction to lorazepam is sedation (15.9%), followed by dizziness (6.9%), weakness (4.2%), and unsteadiness (3.4 reasing the dose. In a sample of about 3,500 anxious patients, the most frequent adverse reaction to lorazepam is sedation (15.9%), followed by dizziness (6.9%), weakness (4.2%), and unsteadiness (3.4%). Less frequent adverse reactions are disorientation, depression, nausea, change in appetite, headache, sleep disturbance, agitation, dermatological symptoms, eye-function disturbance, together with various gastrointestinal symptoms and autonomic manifestations. The incidence of sedation and unsteadiness increased with age. Small decreases in blood pressure have been noted but are not clinically significant, probably being related to the relief of anxiety produced by lorazepam. Transient amnesia or memory impairment has been reported in association with the use of benzodiazepines. Uses temporarily relieves itching Purpose External Analgesic Warnings For external use only. When using this product avoid contact with the eyes. Stop use and ask a doctor if condition worsens, or if symptoms persists for more than 7 days or clear up and occur again within a few days. Do not apply over large areas of the body. Keep out of reach of children. If swallowed, get medical help or contact a Poison Control Center right away. Directions Adults and children 12 years and older: apply a fingertip amount (approximately 1 inch strip) to the affected area not more than 3 to 4 times daily. Children under 12 years: ask a doctor. Stop use and ask a doctor if condition worsens, or if symptoms persists for more than 7 days or clear up and occur again within a few days. Do not apply over large areas of the body. Keep out of reach of children. If swallowed, get medical help or contact a Poison Control Center right away. INDICATIONS & USAGE SECTION Cell Salt; Hemorrhoids; Keloids; Migraine; Nervousness; Constipation before and during menses. OTC - PURPOSE SECTION Cell Salt; Hemorrhoids; Keloids; Migraine; Nervousness; Constipation before and during menses. WARNINGS SECTION WARNINGS: Keep out of reach of children. Do not use if tamper-evident seal is broken or missing. If symptoms worsen or persist for more than a few days, consult a doctor. If pregnant or breast-feeding , ask a doctor before use. DOSAGE & ADMINISTRATION SECTION Directions: Ages 12 and up, take 6 pellets by mouth (ages 0 to 11, give 3 pellets) as needed or as directed by a health professional. Under age 2, crush/dissolve pellets in purified water. Sensitive persons begin with 1 pellet and gradually increase to full dose. OTC - KEEP OUT OF REACH OF CHILDREN SECTION Keep out of reach of children. INDICATIONS & USAGE Ipratropium bromide nasal solution 0.06% (Nasal Spray) is indicated for the symptomatic relief of rhinorrhea associated with the common cold or seasonal allergic rhinitis for adults and children age 5 years and older. Ipratropium bromide nasal solution 0.06% (Nasal Spray) does not relieve nasal congestion or sneezing associated with the common cold or seasonal allergic rhinitis. The safety and effectiveness of the use of ipratropium bromide nasal solution 0.06% (Nasal Spray) beyond four days in patients with the common cold or beyond three weeks in patients with seasonal allergic rhinitis has not been established. WARNINGS Immediate hypersensitivity reactions may occur after administration of ipratropium bromide, as demonstrated by urticaria, angioedema, rash, bronchospasm, anaphylaxis, and oropharyngeal edema. If such a reaction occurs, therapy with ipratropium bromide nasal solution 0.06% (Nasal Spray) should be stopped at once and alternative treatment should be considered. DOSAGE & ADMINISTRATION For Symptomatic Relief of Rhinorrhea Associated with the Common Cold: The recommended dose of ipratropium bromide nasal solution 0.06% (Nasal Spray) is two sprays ( considered. DOSAGE & ADMINISTRATION For Symptomatic Relief of Rhinorrhea Associated with the Common Cold: The recommended dose of ipratropium bromide nasal solution 0.06% (Nasal Spray) is two sprays (84 mcg) per nostril three or four times daily (total dose 504 to 672 mcg/day) in adults and children age 12 years and older. Optimum dosage varies with response of the individual patient. The recommended dose of ipratropium bromide nasal solution 0.06% (Nasal Spray) for children age 5-11 years is two sprays (84 mcg) per nostril three times daily (total dose of 504 mcg/day). The safety and effectiveness of the use of ipratropium bromide nasal solution 0.06% (Nasal Spray) beyond four days in patients with the common cold have not been established. For Symptomatic Relief of Rhinorrhea Associated with Seasonal Allergic Rhinitis: The recommended dose of ipratropium bromide nasal solution 0.06% (Nasal Spray) is two sprays (84 mcg) per nostril four times daily (total dose 672 mcg/day) in adults and children age 5 years and older. The safety and effectiveness of the use of ipratropium bromide nasal solution 0.06% (Nasal Spray) beyond three weeks in patients with seasonal allergic rhinitis have nd children age 5 years and older. The safety and effectiveness of the use of ipratropium bromide nasal solution 0.06% (Nasal Spray) beyond three weeks in patients with seasonal allergic rhinitis have not been established. Initial pump priming requires seven sprays of the pump. If used regularly as recommended, no further priming is required. If not used for more than 24 hours, the pump will require two sprays, or if not used for more than seven days, the pump will require seven sprays to reprime. Avoid spraying into eyes. ADVERSE REACTIONS Adverse reaction information on ipratropium bromide nasal solution 0.06% (Nasal Spray) in patients with the common cold was derived from two multicenter, vehicle-controlled clinical trials involving 1,276 patients (195 patients on ipratropium bromide nasal solution 0.03% (Nasal Spray), 352 patients on ipratropium bromide nasal solution 0.06% (Nasal Spray), 189 patients on ipratropium bromide nasal solution 0.12% (Nasal Spray), 351 patients on vehicle and 189 patients receiving no treatment). Table 1 shows adverse events reported for patients who received ipratropium bromide nasal solution 0.06% (Nasal Spray) at the recommended dose of 84 mcg per e and 189 patients receiving no treatment). Table 1 shows adverse events reported for patients who received ipratropium bromide nasal solution 0.06% (Nasal Spray) at the recommended dose of 84 mcg per nostril, or vehicle, administered three or four times daily, where the incidence is 1% or greater in the ipratropium bromide group and higher in the ipratropium bromide group than in the vehicle group. Table 1 % of Patients with Common Cold Reporting Events * Ipratropium Bromide Nasal Solution 0.06% (Nasal Spray) Vehicle Control No. of Patients 352 351 Epistaxis † 8.2% 2.3% Nasal Dryness 4.8% 2.8% Dry Mouth/Throat 1.4% 0.3% Nasal Congestion 1.1% 0.0% This table includes adverse events for which the incidence was 1% or greater in the ipratropium bromide group and higher in the ipratropium bromide group than in the vehicle group. Epistaxis reported by 5.4% of ipratropium bromide patients and 1.4% of vehicle patients, blood-tinged nasal mucus by 2.8% of ipratropium bromide patients and 0.9% of vehicle patients. Ipratropium bromide nasal solution 0.06% (Nasal Spray) was well tolerated by most patients. The most frequently reported adverse events were transient episodes of nasal dryness or of vehicle patients. Ipratropium bromide nasal solution 0.06% (Nasal Spray) was well tolerated by most patients. The most frequently reported adverse events were transient episodes of nasal dryness or epistaxis. The majority of these adverse events (96%) were mild or moderate in nature, none was considered serious, and none resulted in hospitalization. No patient required treatment for nasal dryness, and only three patients (<1%) required treatment for epistaxis, which consisted of local application of pressure or a moisturizing agent (e.g., petroleum jelly). No patient receiving ipratropium bromide nasal solution 0.06% (Nasal Spray) was discontinued from the trial due to either nasal dryness or bleeding. Adverse events reported by less than 1% of the patients receiving ipratropium bromide nasal solution 0.06% (Nasal Spray) during the controlled clinical trials that are potentially related to ipratropium bromide’s local effects or systemic anticholinergic effects include: taste perversion, nasal burning, conjunctivitis, coughing, dizziness, hoarseness, palpitation, pharyngitis, tachycardia, thirst, tinnitus and blurred vision. No controlled trial was conducted to address the relati ion, nasal burning, conjunctivitis, coughing, dizziness, hoarseness, palpitation, pharyngitis, tachycardia, thirst, tinnitus and blurred vision. No controlled trial was conducted to address the relative incidence of adverse events for three times daily versus four times daily therapy. Nasal adverse events seen in the clinical trial with seasonal allergic rhinitis (SAR) patients (see Table 2) were similar to those seen in the common cold trials. Additional events were reported at a higher rate in the SAR trial due in part to the longer duration of the trial and the inclusion of Upper Respiratory Tract Infection (URI) as an adverse event. In common cold trials, URI was the disease under study and not an adverse event. Table 2 % of Patients with SAR Reporting Events * Ipratropium Bromide Nasal Solution 0.06% (Nasal Spray) Vehicle Control No. of Patients 218 211 Epistaxis † 6.0% 3.3% Pharyngitis 5.0% 3.8% URI 5.0% 3.3% Nasal Dryness 4.6% 0.9% Headache 4.1% 0.5% Dry Mouth/Throat 4.1% 0.0% Taste Perversion 3.7% 1.4% Sinusitis 2.8% 2.8% Pain 1.8% 0.9% Diarrhea 1.8% 0.5% This table includes adverse events for which the incidence was 1% or greater in ipratropium bromide group and higher in aste Perversion 3.7% 1.4% Sinusitis 2.8% 2.8% Pain 1.8% 0.9% Diarrhea 1.8% 0.5% This table includes adverse events for which the incidence was 1% or greater in ipratropium bromide group and higher in the ipratropium bromide group than in the vehicle group. Epistaxis reported by 3.7% of ipratropium bromide patients and 2.4% of vehicle patients, blood tinged nasal mucus by 2.3% of ipratropium bromide patients and 1.9% of vehicle patients. There were no reports of allergic-type reactions in the controlled clinical common cold and SAR trials. Indications To optimize body minerals WARNING If symptoms persist more than a few days, contact a licensed practitioner. As with any other drug, if you are pregnant or nursing a baby, seek the advice of a health care professional before using this product. Keep this and all medications out of the reach of children. In case of accidental overdose, seek professional assistance or contact a Poison Control Center immediately. DOSAGE Adults: take 15 drops twice daily under tongue or diluted in water, unless otherwise recommended by your health professional. Keep this and all medications out of the reach of children. In case of accidental overdose, seek professional assistance or contact a Poison Control Center immediately. INDICATIONS AND USAGE Clindamycin Injection, USP is indicated in the treatment of serious infections caused by susceptible anaerobic bacteria. Clindamycin Injection, USP is also indicated in the treatment of serious infections due to susceptible strains of streptococci, pneumococci, and staphylococci. Its use should be reserved for penicillin-allergic patients or other patients for whom, in the judgment of the physician, a penicillin is inappropriate. Because of the risk of antibiotic-associated pseudomembranous colitis, as described in the WARNING box, before selecting clindamycin the physician should consider the nature of the infection and the suitability of less toxic alternatives (e.g., erythromycin). Bacteriologic studies should be performed to determine the causative organisms and their susceptibility to clindamycin. Indicated surgical procedures should be performed in conjunction with antibiotic therapy. Clindamycin Injection, USP is indicated in the treatment of serious infections caused by susceptible strains of the designated organisms in the conditions listed below: Lower respiratory tract infections including pneumonia, empyema, and lung abscess caused by anaerobes, St ions caused by susceptible strains of the designated organisms in the conditions listed below: Lower respiratory tract infections including pneumonia, empyema, and lung abscess caused by anaerobes, Streptococcus pneumoniae , other streptococci (except E. faecalis ), and Staphylococcus aureus . Skin and skin structure infections caused by Streptococcus pyogenes , Staphylococcus aureus , and anaerobes. Gynecological infections including endometritis, nongonococcal tubo-ovarian abscess, pelvic cellulitis, and postsurgical vaginal cuff infection caused by susceptible anaerobes. Intra-abdominal infections including peritonitis and intra-abdominal abscess caused by susceptible anaerobic organisms. Septicemia caused by Staphylococcus aureus , streptococci (except Enterococcus faecalis ), and susceptible anaerobes. Bone and joint infections including acute hematogenous osteomyelitis caused by Staphylococcus aureus and as adjunctive therapy in the surgical treatment of chronic bone and joint infections due to susceptible organisms. To reduce the development of drug-resistant bacteria and maintain the effectiveness of clindamycin and other antibacterial drugs, clindamycin should be used only fections due to susceptible organisms. To reduce the development of drug-resistant bacteria and maintain the effectiveness of clindamycin and other antibacterial drugs, clindamycin should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy. WARNINGS See WARNING box. Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including clindamycin, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile . C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all pati producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents. If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile , and surgical evaluation should be instituted as clinically indicated. A careful inquiry should be made concerning previous sensitivities to drugs and other allergens. This product contains benzyl alcohol as a preservative. Benzyl alcohol has been associated with a fatal “Gasping Syndrome” in premature infants. (See PRECAUTIONS − Pediatric Use ). Usage in Meningitis: Since clindamycin does not diffuse adequately into the cerebrospinal fluid, the drug should not be used in the treatment of meningitis. SERIOUS ANAPHYLACTOID REACTIONS REQUIRE IMMEDIATE EMERGENCY TREATM nce clindamycin does not diffuse adequately into the cerebrospinal fluid, the drug should not be used in the treatment of meningitis. SERIOUS ANAPHYLACTOID REACTIONS REQUIRE IMMEDIATE EMERGENCY TREATMENT WITH EPINEPHRINE. OXYGEN AND INTRAVENOUS CORTICOSTEROIDS SHOULD ALSO BE ADMINISTERED AS INDICATED. DOSAGE AND ADMINISTRATION If diarrhea occurs during therapy, this antibiotic should be discontinued. (See WARNING box). Adults: Parenteral (I.M. or I.V. Administration): Serious infections due to aerobic gram-positive cocci and the more susceptible anaerobes (NOT generally including Bacteroides fragilis , Peptococcus species and Clostridium species other than Clostridium perfringens ): 600 to 1200 mg/day in 2, 3 or 4 equal doses. More severe infections, particularly those due to proven or suspected Bacteroides fragilis , Peptococcus species, or Clostridium species other than Clostridium perfringens : 1200 to 2700 mg/day in 2, 3 or 4 equal doses. For more serious infections, these doses may have to be increased. In life-threatening situations due to either aerobes or anaerobes, these doses may be increased. Doses of as much as 4800 mg daily have been given intravenously to adults. See y have to be increased. In life-threatening situations due to either aerobes or anaerobes, these doses may be increased. Doses of as much as 4800 mg daily have been given intravenously to adults. See Dilution and Infusion Rates section below. Single I.M. injections of greater than 600 mg are not recommended. Alternatively, drug may be administered in the form of a single rapid infusion of the first dose followed by continuous I.V. infusion as follows: To maintain serum clindamycin levels Above 4 mcg/mL Above 5 mcg/mL Above 6 mcg/mL Rapid infusion rate 10 mg/min for 30 min 15 mg/min for 30 min 20 mg/min for 30 min Maintenance infusion rate 0.75 mg/min 1 mg/min 1.25 mg/min Neonates (less than 1 month): 15 to 20 mg/kg/day in three to four equal doses. The lower dosage may be adequate for small prematures. Pediatric patients (1 month of age to 16 years): Parenteral (I.M. or I.V.) administration: 20 to 40 mg/kg/day in 3 or 4 equal doses. The higher doses would be used for more severe infections. As an alternative to dosing on a body weight basis, pediatric patients may be dosed on the basis of square meters body surface: 350 mg/m 2 /day for serious infections and 450 mg/m 2 /day for mor ions. As an alternative to dosing on a body weight basis, pediatric patients may be dosed on the basis of square meters body surface: 350 mg/m 2 /day for serious infections and 450 mg/m 2 /day for more severe infections. Parenteral therapy may be changed to clindamycin palmitate hydrochloride for oral solution or clindamycin hydrochloride capsules when the condition warrants and at the discretion of the physician. In cases of β-hemolytic streptococcal infections, treatment should be continued for at least 10 days. Dilution and Infusion Rates: Clindamycin phosphate must be diluted prior to I.V. administration. The concentration of clindamycin in diluent for infusion should not exceed 18 mg per mL. Infusion rates should not exceed 30 mg per minute. The usual infusion dilutions and rates are as follows: Dose Diluent Time 300 mg 600 mg 900 mg 1200 mg 50 mL 50 mL 50-100 mL 100 mL 10 min 20 min 30 min 40 min Administration of more than 1200 mg in a single 1-hour infusion is not recommended. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Dilution and Compatibility: Physical and Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Dilution and Compatibility: Physical and biological compatibility studies monitored for 24 hours at room temperature have demonstrated no inactivation or incompatibility with the use of clindamycin phosphate in I.V. solutions containing sodium chloride, glucose, calcium or potassium, and solutions containing vitamin B complex in concentrations usually used clinically. No incompatibility has been demonstrated with the antibiotics cephalothin, kanamycin, gentamicin, penicillin or carbenicillin. The following drugs are physically incompatible with clindamycin phosphate: ampicillin sodium, phenytoin sodium, barbiturates, aminophylline, calcium gluconate, and magnesium sulfate. The compatibility and duration of stability of drug admixtures will vary depending on concentration and other conditions. Physico-Chemical Stability of Diluted Solutions of Clindamycin: Room temperature: 6, 9, and 12 mg/mL (equivalent to clindamycin base) in 5% Dextrose Injection, 0.9% Sodium Chloride Injection, or Lactated Ringer’s Injection in glass bott d Solutions of Clindamycin: Room temperature: 6, 9, and 12 mg/mL (equivalent to clindamycin base) in 5% Dextrose Injection, 0.9% Sodium Chloride Injection, or Lactated Ringer’s Injection in glass bottles or minibags, demonstrated physical and chemical stability for at least 16 days at 25°C. Also, 18 mg/mL (equivalent to clindamycin base) in 5% Dextrose Injection, in minibags, demonstrated physical and chemical stability for at least 16 days at 25°C. Refrigeration: 6, 9 and 12 mg/mL (equivalent to clindamycin base) in 5% Dextrose Injection, 0.9% Sodium Chloride Injection, or Lactated Ringer’s Injection in glass bottles or minibags, demonstrated physical and chemical stability for at least 32 days at 4°C. IMPORTANT: This chemical stability information in no way indicates that it would be acceptable practice to use this product well after the preparation time. Good professional practice suggests that compounded admixtures should be administered as soon after preparation as is feasible. Frozen: 6, 9 and 12 mg/mL (equivalent to clindamycin base) in 5% Dextrose Injection, 0.9% Sodium Chloride Injection, or Lactated Ringer’s Injection in minibags demonstrated physical and chemical stabili ozen: 6, 9 and 12 mg/mL (equivalent to clindamycin base) in 5% Dextrose Injection, 0.9% Sodium Chloride Injection, or Lactated Ringer’s Injection in minibags demonstrated physical and chemical stability for at least eight weeks at -10°C. Frozen solutions should be thawed at room temperature and not refrozen. Caution: Do not use plastic containers in series connections. Such use could result in air embolism due to residual air being drawn from the primary container before administration of the fluid from the secondary container is complete. ADVERSE REACTIONS The following reactions have been reported with the use of clindamycin. Gastrointestinal: Antibiotic-associated colitis (see WARNINGS ), pseudomembranous colitis abdominal pain, nausea and vomiting. The onset of pseudomembranous colitis symptoms may occur during or after antibacterial treatment (see WARNINGS ). An unpleasant or metallic taste occasionally has been reported after intravenous administration of the higher doses of clindamycin phosphate. Hypersensitivity Reactions: Maculopapular rash and urticaria have been observed during drug therapy. Generalized mild to moderate morbilliform-like skin rashes are the most frequent damycin phosphate. Hypersensitivity Reactions: Maculopapular rash and urticaria have been observed during drug therapy. Generalized mild to moderate morbilliform-like skin rashes are the most frequently reported of all adverse reactions. Rare instances of erythema multiforme, some resembling Stevens-Johnson syndrome, have been associated with clindamycin. A few cases of anaphylactoid reactions have been reported. If a hypersensitivity reaction occurs, the drug should be discontinued. The usual agents (epinephrine, corticosteroids, antihistamines) should be available for emergency treatment of serious reactions. Skin and Mucous Membranes: Pruritus, vaginitis, and rare instances of exfoliative dermatitis have been reported. (See Hypersensitivity Reactions ). Liver: Jaundice and abnormalities in liver function tests have been observed during clindamycin therapy. Renal: Although no direct relationship of clindamycin to renal damage has been established, renal dysfunction as evidenced by azotemia, oliguria, and/or proteinuria has been observed in rare instances. Hematopoietic: Transient neutropenia (leukopenia) and eosinophilia have been reported. Reports of agranulocytosis and thromboc otemia, oliguria, and/or proteinuria has been observed in rare instances. Hematopoietic: Transient neutropenia (leukopenia) and eosinophilia have been reported. Reports of agranulocytosis and thrombocytopenia have been made. No direct etiologic relationship to concurrent clindamycin therapy could be made in any of the foregoing. Local Reactions: Pain, induration and sterile abscess have been reported after intramuscular injection and thrombophlebitis after intravenous infusion. Reactions can be minimized or avoided by giving deep intramuscular injections and avoiding prolonged use of indwelling intravenous catheters. Musculoskeletal: Rare instances of polyarthritis have been reported. Cardiovascular: Rare instances of cardiopulmonary arrest and hypotension have been reported following too rapid intravenous administration. (See DOSAGE AND ADMINISTRATION ). USE: hand sanitizer to help reduce bacteria on the skin that may cause disease. Purpose Antimicrobial Warnings: for external use only. Flammable. Keep away from heat and flame. When using this product avoid contact with face, eyes, and broken skin. In case of eye contact, flush with plenty of water and seek medical advice. Stop use and ask a doctor if irritation or redness develops. Keep out of reach of children. if swallowed, get medical help or contact a Poison Control Center. Directions wet hands thoroughly with product and rub into skin until dry. children under 6 years of age should be supervised by an adult when using. Stop use and ask a doctor if irritation or redness develops. Keep out of reach of children. if swallowed, get medical help or contact a Poison Control Center. Directions: FOR ORAL USE. Use: Temporary relief of headache. Warnings: Claims based on traditional homeopathic practice, not accepted medical evidence. Not FDA evaluated. Do not use if allergic to any ingredient. Consult a doctor before use for serious conditions or if conditions worsen or persist. If pregnant or nursing, consult a doctor before use. Not for injection. Take the contents of one ampule under the tongue and hold for 30 seconds, then swallow. KEEP OUT OF REACH OF CHILDREN. Uses: Homeopathic medicine for temporary relief of sciatic pain and pressure Reduces occasional pain, pressure and inflammation from sciatica Warnings: If symptoms persist or worsen, consult a healthcare professional Directions: For all ages: Mix 0.50 mL in 1/4 cup of water and sip slowly. Repeat 3-5 times daily. For acute symptoms, repeat every 30 minutes as needed until symptoms subside, or up to 48 hours. If preferred, drops may be taken directly in the mounth Keep this and all medication out of reach of children Use reduces underarm wetness Purpose Antiperspirant Warnings For external use only. Flammable • do not spray near flame or while smoking • contents under pressure • do not crush, puncture or incinerate • do not store at temperature above 120°F Do not use on broken skin Ask a doctor before use if you have kidney disease When using this product • keep away from face and mouth to avoid breathing it • avoid spraying in eyes • use only as directed; intentional misuse by deliberately concentrating and inhaling the contents can be harmful or fatal Stop use if rash or irritation occurs Keep out of reach of children. lf swallowed, get medical help or contact a Poison Control Center right away. Directions • apply to underarms only • hold can about 6 inches away from underarm and spray. Ask a doctor before use if you have kidney disease Stop use if rash or irritation occurs Keep out of reach of children. lf swallowed, get medical help or contact a Poison Control Center right away. 1 INDICATIONS AND USAGE Betamethasone dipropionate cream (augmented) is a corticosteroid indicated for the relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses in patients 13 years of age or older. Betamethasone dipropionate cream (augmented), 0.05% is a corticosteroid indicated for the relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses in patients 13 years of age and older. ( 1 ) 2 DOSAGE AND ADMINISTRATION Apply a thin film of betamethasone dipropionate cream (augmented) to the affected skin areas once or twice daily. Therapy should be discontinued when control is achieved. Betamethasone dipropionate cream (augmented) is a high-potency corticosteroid. Treatment with betamethasone dipropionate cream (augmented) should not exceed 50 g per week because of the potential for the drug to suppress the hypothalamic-pituitary-adrenal (HPA) axis [see Warnings and Precautions (5.1) ]. Betamethasone dipropionate cream (augmented) should not be used with occlusive dressings unless directed by a physician. Avoid contact with eyes. Wash hands after each application. Avoid use on the face, groin, or axillae, or e cream (augmented) should not be used with occlusive dressings unless directed by a physician. Avoid contact with eyes. Wash hands after each application. Avoid use on the face, groin, or axillae, or if skin atrophy is present at the treatment site. Betamethasone dipropionate cream (augmented) is for topical use only. It is not for oral, ophthalmic, or intravaginal use. Apply a thin film to the affected skin areas once or twice daily. ( 2 ) Discontinue therapy when control is achieved. ( 2 ) Use no more than 50 g per week. ( 2 ) Do not use with occlusive dressings unless directed by a physician. ( 2 ) Avoid use on the face, groin, or axillae, or if skin atrophy is present at the treatment site. ( 2 ) Not for oral, ophthalmic, or intravaginal use. ( 2 ) 6 ADVERSE REACTIONS The most common adverse reaction reported in 0.4% of adult patients is stinging. ( 6.1 ) The most common adverse reactions reported in 10% of pediatric patients are signs of skin atrophy, telangiectasia, bruising, shininess. ( 6.1 , 8.4 ) To report SUSPECTED ADVERSE REACTIONS, contact Sun Pharmaceutical Industries, Inc., at 1-866-923-4914 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Exper ininess. ( 6.1 , 8.4 ) To report SUSPECTED ADVERSE REACTIONS, contact Sun Pharmaceutical Industries, Inc., at 1-866-923-4914 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience 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 clinical practice. In controlled clinical trials, involving 242 adult subjects, the adverse reaction associated with the use of betamethasone dipropionate cream (augmented) reported at a frequency of 0.4% was stinging. It occurred in 1 subject. In a controlled clinical trial involving 67 pediatric subjects from 3 months to 12 years of age, the adverse reactions associated with the use of betamethasone dipropionate cream (augmented) occurred in 7 of 67 (10%) subjects. Reported reactions included signs of skin atrophy (telangiectasia, bruising, shininess). 6.2 Postmarketing Experience Because adverse reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency ruising, shininess). 6.2 Postmarketing Experience Because adverse 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. Postmarketing reports for local adverse reactions to topical corticosteroids may also include: burning, itching, irritation, dryness, folliculitis, acneiform eruptions, hypopigmentation, perioral dermatitis, allergic contact dermatitis, secondary infection, hypertrichosis, skin atrophy, striae, and miliaria. Hypersensitivity reactions, consisting of predominantly skin signs and symptoms, e.g., contact dermatitis, pruritus, bullous dermatitis, and erythematous rash have been reported. Ophthalmic adverse reactions of cataracts, glaucoma, increased intraocular pressure, and central serous chorioretinopathy have been reported with the use of topical corticosteroids, including topical betamethasone products. Use to decrease bacteria on the skin that could cause disease recommended for repeated use purpose Antiseptic Warnings For external use only: hands Flammable. Keep away from fire or flame. Directions wet hands thoroughly with product and allow to dry without wiping for children under 6, use only under adult suervision not recommended for infants REF HH62G02UMC www.medline.com Made in USA with US and Foreign components for Medline industries, Inc., Northfield, IL 60093 USA 1-800-MEDLINE RG17VJO Stop use and ask a doctor if irritation or redness develops condition persists for more than 72 hours Keep out of reach children If swallowed, get medical help or contact a Poison Control Center right away. INDICATIONS AND USAGE Carefully consider the potential benefits and risks of etodolac and other treatment options before deciding to use etodolac. Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals (see WARNINGS ). Etodolac tablets, USP are indicated: For acute and long-term use in the management of signs and symptoms of the following: Osteoarthritis Rheumatoid arthritis For the management of acute pain 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, including myocardial infarction (MI) and stroke, which can be fatal. Based on available data, it is unclear that the risk for CV thrombotic events is similar for all NSAIDs. The relative increase in serious CV thrombotic events over baseline conferred by NSAID use appears to be similar in those with and without known CV disease or risk factors for CV disease. However, patients with known CV disease or risk factors had a higher absolute incidence of excess serious CV thrombotic events, due to with and without known CV disease or risk factors for CV disease. However, patients with known CV disease or risk factors had a higher absolute incidence of excess serious CV thrombotic events, due to their increased baseline rate. Some observational studies found that this increased risk of serious CV thrombotic events began as early as the first weeks of treatment. The increase in CV thrombotic risk has been observed most consistently at higher doses. To minimize the potential risk for an adverse CV event in NSAID-treated patients, use the lowest effective dose for the shortest duration possible. Physicians and patients should remain alert for the development of such events, throughout the entire treatment course, even in the absence of previous CV symptoms. Patients should be informed about the symptoms of serious CV events and the steps to take if they occur. There is no 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, such as etodolac, increases the risk of serious gastrointestinal (GI) events (see WARNINGS ). Status Post Coronary Artery Bypass associated with NSAID use. The concurrent use of aspirin and an NSAID, such as etodolac, increases the risk of serious gastrointestinal (GI) events (see WARNINGS ). Status Post Coronary Artery Bypass Graft (CABG) Surgery Two large, controlled clinical trials of a COX-2 selective NSAID for the treatment of pain in the first 10 to 14 days following CABG surgery found an increased incidence of myocardial infarction and stroke. NSAIDs are contraindicated in the setting of CABG (see CONTRAINDICATIONS ). Post-MI Patients Observational studies conducted in the Danish National Registry have demonstrated that patients treated with NSAIDs in the post-MI period were at increased risk of reinfarction, CV-related death, and all-cause mortality beginning in the first week of treatment. In this same cohort, the incidence of death in the first year post MI was 20 per 100 person years in NSAID-treated patients compared to 12 per 100 person years in non-NSAID exposed patients. Although the absolute rate of death declined somewhat after the first year post-MI, the increased relative risk of death in NSAID users persisted over at least the next four years of follow-up. Avoid the use of etodolac in pat of death declined somewhat after the first year post-MI, the increased relative risk of death in NSAID users persisted over at least the next four years of follow-up. Avoid the use of etodolac in patients with a recent MI unless the benefits are expected to outweigh the risk of recurrent CV thrombotic events. If etodolac is used in patients with a recent MI, monitor patients for signs of cardiac ischemia. Hypertension NSAIDs, including etodolac, 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 etodolac, 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. Heart Failure and Edema The Coxib and traditional NSAID Trialists’ Collaboration meta-analysis of randomized controlled trials demonstrated an approximately two-fold increase in hospitalizations for heart failure in COX-2 selective-treated patients and nonselective NSAID- boration meta-analysis of randomized controlled trials demonstrated an approximately two-fold increase in hospitalizations for heart failure in COX-2 selective-treated patients and nonselective NSAID-treated patients compared to placebo-treated patients. In a Danish National Registry study of patients with heart failure, NSAID use increased the risk of MI, hospitalization for heart failure, and death. Additionally, fluid retention and edema have been observed in some patients treated with NSAIDs. Use of etodolac may blunt the CV effects of several therapeutic agents used to treat these medical conditions [e.g., diuretics, ACE inhibitors, or angiotensin receptor blockers (ARBs)] (see Drug Interactions ). Avoid the use of etodolac in patients with severe heart failure unless the benefits are expected to outweigh the risk of worsening heart failure. If etodolac is used in patients with severe heart failure, monitor patients for signs of worsening heart failure. Gastrointestinal (GI) Effects - Risk of GI Ulceration, Bleeding, and Perforation NSAIDs, including etodolac, can cause serious gastrointestinal (GI) adverse events including inflammation, bleeding, ulceration, and perforation o ts - Risk of GI Ulceration, Bleeding, and Perforation NSAIDs, including etodolac, 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 to 6 months, and in about 2% to 4% of patients treated for 1 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. Physicians should inform patients about the signs and/or symptoms of serious GI toxicity and what steps to take if they occur. 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/o f they occur. 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, and who use NSAIDs have a greater than 10-fold risk for developing a GI bleed than patients with neither of these risk factors. Other factors that increase the risk for 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 of debilitated patients, and therefore, special care should be taken in treating this population. To minimize the potential risk for an adverse GI event, the lowest effective dose should be used for the shortest possible duration. Patients and physicians should remain alert for signs and symptoms of GI ulceration and bleeding during NSAID therapy and promptly initiate additional evaluation and treatment if a serious GI adverse event is suspected. This should include discontinuation of the NSAID until a serious GI adverse eve ring NSAID therapy and promptly initiate additional evaluation and treatment if a serious GI adverse 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 nonsteroidal anti-inflammatory drug may cause a dose-dependent reduction in prostaglandin formation and, secondarily, in renal blood flow, which may precipitate overt renal decompensation. Patients at a greater 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. Renal pelvic transitional epithelial hyperplasia, a spontaneous change occurring with variable frequency, was observed with increased frequ y is usually followed by recovery to the pretreatment state. Renal pelvic transitional epithelial hyperplasia, a spontaneous change occurring with variable frequency, was observed with increased frequency in treated male rats in a 2-year chronic study. Advanced Renal Disease No information is available from controlled clinical studies regarding the use of etodolac in patients with advanced renal disease. Therefore, treatment with etodolac is not recommended in these patients with advanced renal disease. If etodolac therapy must be initiated, close monitoring of the patient’s renal function is advisable. Anaphylactoid Reactions As with other NSAIDS, anaphylactoid reactions may occur in patients without prior exposure to etodolac. Etodolac 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. Fatal reactions have been reported in such patients (see CONTRAINDICATIONS and PRECAUTIONS , General , Pre-existing Asthma ). Emergency help should be sought in cases where an anaphylactoid r NSAIDs. Fatal reactions have been reported in such patients (see CONTRAINDICATIONS and PRECAUTIONS , General , Pre-existing Asthma ). Emergency help should be sought in cases where an anaphylactoid reaction occurs. Skin Reactions NSAIDs, including etodolac, 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, the third trimester, as with other NSAIDs, etodolac should be avoided because it may cause premature closure of the ductus arteriosus (see PRECAUTIONS , Pregnancy , Non-teratogenic Effects ). DOSAGE AND ADMINISTRATION Carefully consider the potential benefits and risks of etodolac and other treatment options before deciding to use etodolac. Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals (see WARNINGS ). After observing the response tment options before deciding to use etodolac. Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals (see WARNINGS ). After observing the response to the initial therapy with etodolac, the dose and frequency should be adjusted to suit an individual patient's needs. Dosage adjustment of etodolac is generally not required in patients with mild to moderate renal impairment. Etodolac should be used with caution in such patients, because, as with other NSAIDs, it may further decrease renal function in some patients with impaired renal function (see WARNINGS, Renal Effects ). Analgesia The recommended total daily dose of etodolac for acute pain is up to 1,000 mg, given as 200 to 400 mg every 6 to 8 hours. Doses of etodolac greater than 1,000 mg/day have not been adequately evaluated in well-controlled clinical trials. Osteoarthritis and Rheumatoid Arthritis The recommended starting dose of etodolac for the management of the signs and symptoms of osteoarthritis or rheumatoid arthritis is: 300 mg b.i.d., t.i.d., or 400 mg b.i.d., or 500 mg b.i.d. A lower dose of 600 mg/day may suffice for long-term administration. Physicians should be aw oms of osteoarthritis or rheumatoid arthritis is: 300 mg b.i.d., t.i.d., or 400 mg b.i.d., or 500 mg b.i.d. A lower dose of 600 mg/day may suffice for long-term administration. Physicians should be aware that doses above 1,000 mg/day have not been adequately evaluated in well-controlled clinical trials. In chronic conditions, a therapeutic response to therapy with etodolac is sometimes seen within one week of therapy, 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. ADVERSE REACTIONS In patients taking etodolac or other NSAIDs, the most frequently reported adverse experiences occurring in approximately 1 to 10% of patients are: Gastrointestinal experiences including : abdominal pain, constipation, diarrhea, dyspepsia, flatulence, gross bleeding/perforation, heartburn, nausea, GI ulcers (gastric/duodenal), vomiting. Other events including : abnormal renal function, anemia, dizziness, edema, elevated liver enzymes, headaches, increased bleeding time, pruritis, rashes, tinnitus. Adverse-reaction information for etodolac was derived from 2,629 arthritic patients treated with etodola edema, elevated liver enzymes, headaches, increased bleeding time, pruritis, rashes, tinnitus. Adverse-reaction information for etodolac was derived from 2,629 arthritic patients treated with etodolac in double-blind and open-label clinical trials of 4 to 320 weeks in duration and worldwide postmarketing surveillance studies. In clinical trials, most adverse reactions were mild and transient. The discontinuation rate in controlled clinical trials, because of adverse events, was up to 10% for patients treated with etodolac. New patient complaints (with an incidence greater than or equal to 1%) are listed below by body system. The incidences were determined from clinical trials involving 465 patients with osteoarthritis treated with 300 to 500 mg of etodolac b.i.d. (i.e., 600 to 1,000 mg/day). Incidence Greater Than Or Equal To 1% - Probably Causally Related Body as a whole - Chills and fever. Digestive system - Dyspepsia (10%), abdominal pain*, diarrhea*, flatulence*, nausea*, constipation, gastritis, melena, vomiting. Nervous system - Asthenia/malaise*, dizziness*, depression, nervousness. Skin and appendages - Pruritus, rash. Special senses - Blurred vision, tinnitus. Urogenital tion, gastritis, melena, vomiting. Nervous system - Asthenia/malaise*, dizziness*, depression, nervousness. Skin and appendages - Pruritus, rash. Special senses - Blurred vision, tinnitus. Urogenital system - Dysuria, urinary frequency. * Drug-related patient complaints occurring in 3 to 9% of patients treated with etodolac. Drug-related patient-complaints occurring in fewer than 3%, but more than 1%, are unmarked. Incidence Less Than 1% - Probably Causally Related (Adverse reactions reported only in worldwide postmarketing experience, not seen in clinical trials, are considered rarer and are italicized.) Body as a whole - Allergic reaction, anaphylactic/anaphylactoid reactions (including shock). Cardiovascular system - Hypertension, congestive heart failure, flushing, palpitations, syncope, vasculitis (including necrotizing and allergic). Digestive system - Thirst, dry mouth, ulcerative stomatitis, anorexia, eructation, elevated liver enzymes, cholestatic hepatitis, hepatitis, cholestatic jaundice, duodenitis, jaundice, hepatic failure, liver necrosis, peptic ulcer with or without bleeding and/or perforation , intestinal ulceration, pancreatitis. Hemic and lymphatic system - Ecchy atic jaundice, duodenitis, jaundice, hepatic failure, liver necrosis, peptic ulcer with or without bleeding and/or perforation , intestinal ulceration, pancreatitis. Hemic and lymphatic system - Ecchymosis, anemia, thrombocytopenia, bleeding time increased, agranulocytosis, hemolytic anemia, leukopenia, neutropenia, pancytopenia. Metabolic and nutritional - Edema, serum creatinine increase, hyperglycemia in previously controlled diabetic patients. Nervous system - Insomnia, somnolence. Respiratory system - Asthma, pulmonary infiltration with eosinophilia. Skin and appendages - Angioedema, sweating, urticaria, vesiculobullous rash, cutaneous vasculitis with purpura, Stevens-Johnson Syndrome, toxic epidermal necrolysis , hyperpigmentation , erythema multiforme. Special senses - Photophobia, transient visual disturbances. Urogenital system - Elevated BUN, renal failure, renal insufficiency, renal papillary necrosis. Incidence Less Than 1% - Causal Relationship Unknown (Medical events occurring under circumstances where causal relationship to etodolac is uncertain. These reactions are listed as alerting information for physicians.) Body as a whole - Infection, headache. Cardiovascular rring under circumstances where causal relationship to etodolac is uncertain. These reactions are listed as alerting information for physicians.) Body as a whole - Infection, headache. Cardiovascular system - Arrhythmias, myocardial infarction, cerebrovascular accident. Digestive system - Esophagitis with or without stricture or cardiospasm, colitis. Metabolic and nutritional - Change in weight. Nervous system - Paresthesia, confusion. Respiratory system - Bronchitis, dyspnea, pharyngitis, rhinitis, sinusitis. Skin and appendages - Alopecia, maculopapular rash, photosensitivity, skin peeling. Special senses - Conjunctivitis, deafness, taste perversion. Urogenital system - Cystitis, hematuria, leukorrhea, renal calculus, interstitial nephritis, uterine bleeding irregularities. Additional Adverse Reactions Reported with NSAIDS Body as a whole - Sepsis, death Cardiovascular system - Tachycardia Digestive system - Gastric ulcers, gastritis, gastrointestinal bleeding, glossitis, hematemesis Hemic and lymphatic system - Lymphadenopathy Nervous system - Anxiety, dream abnormalities, convulsions, coma, hallucinations, meningitis, tremors, vertigo Respiratory system - Respiratory depression Hemic and lymphatic system - Lymphadenopathy Nervous system - Anxiety, dream abnormalities, convulsions, coma, hallucinations, meningitis, tremors, vertigo Respiratory system - Respiratory depression, pneumonia Urogenital system - Oliguria/polyuria, proteinuria Use: Antiseptic skin preparation Purpose: Antiseptic Warnings: Do not use if allergic to iodine For external use only Do not use in eyes Avoid pooling beneath patient. Prolonged exposure to wet solution may cause skiin irritation. Directions: Apply locally as needed. Ask a doctor before use if injuries are deep or puncture wounds Serious burns Stop use and ask a doctor if Redness, irritation, swelling or pain persisits or increases Infection occurs Keep out of reach of children. In case of a accidental ingestion,, seek professional assistance or consult a poison control center immediately 1 INDICATIONS AND USAGE Calcium acetate is a phosphate binder indicated to reduce serum phosphorus in patients with end stage renal disease (ESRD). Calcium acetate is a phosphate binder indicated for the reduction of serum phosphorus in patients with end stage renal disease. ( 1 ) 2 DOSAGE AND ADMINISTRATION The recommended initial dose of calcium acetate for the adult dialysis patient is 2 capsules with each meal. Increase the dose gradually to lower serum phosphorus levels to the target range, as long as hypercalcemia does not develop. Most patients require 3-4 capsules with each meal. Starting dose is 2 capsules with each meal. (2) Titrate the dose every 2-3 weeks until acceptable serum phosphorus level is reached. Most patients require 3-4 capsules with each meal. (2) 6 ADVERSE REACTIONS Hypercalcemia is discussed elsewhere [see Warnings and Precautions (5.1) ]. The most common (>10%) adverse reactions are hypercalcemia, nausea and vomiting. ( 6.1 ) In clinical studies, patients have occasionally experienced nausea during calcium acetate therapy. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Cipla Ltd. at 1-866-604-3268 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch 6. ve occasionally experienced nausea during calcium acetate therapy. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Cipla Ltd. at 1-866-604-3268 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch 6.1 Clinical Trial Experience 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. In clinical studies, calcium acetate has been generally well tolerated. Calcium acetate was studied in a 3-month, open-label, non-randomized study of 98 enrolled ESRD hemodialysis patients and an alternate liquid formulation of calcium acetate was studied in a two week double-blind, placebo-controlled, cross-over study with 69 enrolled ESRD hemodialysis patients. Adverse reactions (>2% on treatment) from these trials are presented in Table 1. Table 1: Adverse Reactions in Patients with End-Stage Renal Disease Undergoing Hemodialysis Preferred Term Total adverse reactions reported for calcium acetate n=167 n (%) 3-month, open-label study of calcium acetate n=98 n (%) Double blind, placebo-controlled, isease Undergoing Hemodialysis Preferred Term Total adverse reactions reported for calcium acetate n=167 n (%) 3-month, open-label study of calcium acetate n=98 n (%) Double blind, placebo-controlled, cross-over study of liquid calcium acetate n=69 Calcium acetate n (%) Placebo n (%) Nausea 6 (3.6) 6 (6.1) 0(0.0) 0(0.0) Vomiting 4 (2.4) 4 (4.1) 0(0.0) 0(0.0) Hypercalcemia 21 (12.6) 16 (16.3) 5 (7.2) 0(0.0) Mild hypercalcemia may be asymptomatic or manifest itself as constipation, anorexia, nausea, and vomiting. More severe hypercalcemia is associated with confusion, delirium, stupor, and coma. Decreasing dialysate calcium concentration could reduce the incidence and severity of calcium acetate - induced hypercalcemia. Isolated cases of pruritus have been reported, which may represent allergic reactions. 6.2 Postmarketing Experience Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to estimate their frequency or to establish a causal relationship to drug exposure. The following additional adverse reactions have been identified during post-approval of calcium acetate: dizziness, edema, and weakness. Uses Uses: Firming & Nourishing PURPOSE Purpose: Humectant WARNINGS Warnings: For external use only 1. When you feel irregular response on the applied area such as red spots, swollen skin, itching or rash caused by exposure to direct sunlight, please consult a dermatologist 2. Do not apply to the areas of skin with wounds or other skin problems 3. Cautions on storage 1) Keep out of the reach of children 2) Do not store in direct sunlight Directions Directions: Apply mask and leave on for 10-20 minutes. KEEP OUT OF REACH OF CHILDREN KEEP OUT OF REACH OF CHILDREN Purpose: To help alleviate the symptoms of grief. Uses: To help alleviate the symptoms of grief. Warning: If pregnant or breast-feeding, ask a health professional before use. Keep out of reach of children. In case of overdose, get medical help or contact a Poison Control Center right away. Use only as directed. Directions: 10 drops orally, 3 times a day or a directed by a health care professional. Keep out of reach of children. In case of overdose, get medical help or contact a Poison Control Center right away. USES This homeopathic medicine helps relieve symptoms of eczema: - dry skin - body rashes - cracked skin - itching PURPOSE dry scaly skin dry and cracked skin, body rash itching and redness intense itching behind the ears, redness, dry and cracked skin itching dry skin and itching itching rash WARNINGS Stop use and ask a doctor if symptoms worsen or persist for more than 7 days. If pregnant or breast-feeding , ask a health professional before use. Keep out of reach of children. DIRECTIONS Chew tablets and let dissolve in mouth. Do not use more than directed. Do not take with food. Repeat 3 times daily and reduce intake with improvement or as directed by a health professional. Age Dose Adults and children 12 years of age and older 2 tablets Children 2 to 11 years of age 1 tablet Children under 2 years of age Ask a doctor Stop use and ask a doctor if symptoms worsen or persist for more than 7 days. Keep out of reach of children. 1 INDICATIONS AND USAGE ENTRESTO is a combination of sacubitril, a neprilisin inhibitor, and valsartan, an angiotensin II receptor blocker, and is indicated: to reduce the risk of cardiovascular death and hospitalization for heart failure in adult patients with chronic heart failure. Benefits are most clearly evident in patients with left ventricular ejection fraction (LVEF) below normal. ( 1.1 ) for the treatment of symptomatic heart failure with systemic left ventricular systolic dysfunction in pediatric patients aged one year and older. ENTRESTO reduces NT-proBNP and is expected to improve cardiovascular outcomes. ( 1.2 ) 1.1 Adult Heart Failure ENTRESTO is indicated to reduce the risk of cardiovascular death and hospitalization for heart failure in adult patients with chronic heart failure. Benefits are most clearly evident in patients with left ventricular ejection fraction (LVEF) below normal. LVEF is a variable measure, so use clinical judgment in deciding whom to treat [see Clinical Studies (14.1)] . 1.2 Pediatric Heart Failure ENTRESTO is indicated for the treatment of symptomatic heart failure with systemic left ventricular systolic dysfunction in pediatric patients aged nical Studies (14.1)] . 1.2 Pediatric Heart Failure ENTRESTO is indicated for the treatment of symptomatic heart failure with systemic left ventricular systolic dysfunction in pediatric patients aged one year and older. ENTRESTO reduces NT-proBNP and is expected to improve cardiovascular outcomes. 2 DOSAGE AND ADMINISTRATION The recommended starting dosage for adults is 49 mg/51 mg orally twice daily. The target maintenance dose is 97 mg/103mg orally twice daily. ( 2.2 ) Adjust adult doses every 2 to 4 weeks to the target maintenance dose, as tolerated by the patient. ( 2.2 ) For pediatric patients, see the Full Prescribing Information for recommended dosage, titrations, preparation and administration instructions. ( 2.3 , 2.4 , 2.5 ) Reduce starting dose to half the usually recommended starting dosage for: patients not currently taking an angiotensin-converting enzyme (ACE) inhibitor or angiotensin II receptor blocker (ARB) or previously taking a low dose of these agents. ( 2.6 ) patients with severe renal impairment. ( 2.7 ) patients with moderate hepatic impairment. ( 2.8 ) 2.1 General Considerations ENTRESTO is contraindicated with concomitant use of an angiotensin-converting e ents with severe renal impairment. ( 2.7 ) patients with moderate hepatic impairment. ( 2.8 ) 2.1 General Considerations ENTRESTO is contraindicated with concomitant use of an angiotensin-converting enzyme (ACE) inhibitor. If switching from an ACE inhibitor to ENTRESTO allow a washout period of 36 hours between administration of the two drugs [see Contraindications (4) and Drug Interactions (7.1)] . 2.2 Adult Heart Failure The recommended starting dose of ENTRESTO is 49/51 mg orally twice-daily. Double the dose of ENTRESTO after 2 to 4 weeks to the target maintenance dose of 97/103 mg twice daily, as tolerated by the patient. 2.3 Pediatric Heart Failure For the recommended dosage for pediatric patients aged 1 year and older, refer to Table 1 if using the tablets, or Table 2 if using the oral pellets. Take the recommended dose orally twice daily. Adjust pediatric patient doses every 2 weeks, as tolerated by the patient. Table 1: Recommended Dose and Titration for Pediatric Patients Using Tablets † Use of the oral suspension or oral pellets (see Table 2) is recommended in these patients. Recommended mg/kg doses are of the combined amount of both sacubitril and valsartan [see Dosage a g Tablets † Use of the oral suspension or oral pellets (see Table 2) is recommended in these patients. Recommended mg/kg doses are of the combined amount of both sacubitril and valsartan [see Dosage and Administration (2.4, 2.5)] . ‡ Doses of 72 mg/78 mg can be achieved using three 24 mg/26 mg tablets [see Dosage Forms and Strengths (3)] . Titration Step Dose (twice daily) Weight (kg) Starting Second Final Less than 40 kg † 1.6 mg/kg 2.3 mg/kg 3.1 mg/kg At least 40 kg, less than 50 kg 24 mg/26 mg 49 mg/51 mg 72 mg/78 mg ‡ At least 50 kg 49 mg/51 mg 72 mg/78 mg ‡ 97 mg/103 mg Table 2: Recommended Dose and Titration for Pediatric Patients using ENTRESTO SPRINKLE † † When using capsules, more than one capsule may be needed to achieve recommended doses. Oral pellets are contained within each capsule. Use the entire contents of the capsules to achieve the dose. ‡ Recommended mg/kg doses are of the combined amount of sacubitril and valsartan [see Dosage and administration (2.4)] . * For patients 50 kg or more, see Table 1. Titration Step Dose (twice daily) Weight (kg) * Starting Second Final Less than 13 (use oral suspension ‡ ) 1.6 mg/kg 2.3 mg/kg 3.1 mg/kg 13 to less than 19 12 mg/12 m ents 50 kg or more, see Table 1. Titration Step Dose (twice daily) Weight (kg) * Starting Second Final Less than 13 (use oral suspension ‡ ) 1.6 mg/kg 2.3 mg/kg 3.1 mg/kg 13 to less than 19 12 mg/12 mg (Two 6 mg/6 mg capsules) 18 mg/18 mg (Three 6 mg/6 mg capsules) 24 mg/24 mg (Four 6 mg/6 mg capsules) 19 to less than 26 18 mg/18 mg (Three 6 mg/6 mg capsules) 24 mg/24 mg (Four 6 mg/6 mg capsules) 30 mg/32 mg (Two 15 mg/16 mg capsules) 26 to less than 34 24 mg/24 mg (Four 6 mg/6 mg capsules) 30 mg/32 mg (Two 15 mg/16 mg capsules) 45 mg/48 mg (Three 15 mg/16 mg capsules) 34 to less than 50 * 30 mg/32 mg (Two 15 mg/16 mg capsules) 45 mg/48 mg (Three 15 mg/16 mg capsules) 60 mg/64 mg (Four 15 mg/16 mg capsules) 2.4 Preparation of Oral Suspension Using Tablets ENTRESTO oral suspension can be substituted at the recommended tablet dosage in patients unable to swallow tablets. ENTRESTO 800 mg/200 mL oral suspension can be prepared in a concentration of 4 mg/mL (sacubitril/valsartan 1.96/2.04 mg/mL). Use ENTRESTO 49/51 mg tablets in the preparation of the suspension. To make an 800 mg/200 mL (4 mg/mL) oral suspension, transfer eight tablets of ENTRESTO 49/51 mg film-coated tablets into a mo g/mL). Use ENTRESTO 49/51 mg tablets in the preparation of the suspension. To make an 800 mg/200 mL (4 mg/mL) oral suspension, transfer eight tablets of ENTRESTO 49/51 mg film-coated tablets into a mortar. Crush the tablets into a fine powder using a pestle. Add 60 mL of Ora-Plus ® into the mortar and triturate gently with pestle for 10 minutes, to form a uniform suspension. Add 140 mL of Ora-Sweet ® SF into mortar and triturate with pestle for another 10 minutes, to form a uniform suspension. Transfer the entire contents from the mortar into a clean 200 mL amber colored PET or glass bottle. Place a press-in bottle adapter and close the bottle with a child resistant cap. The oral suspension can be stored for up to 15 days. Do not store above 25°C (77°F) and do not refrigerate. Shake before each use. * Ora-Sweet SF ® and Ora-Plus ® are registered trademarks of Paddock Laboratories, Inc. 2.5 Preparation and Administration of Oral Pellets ENTRESTO SPRINKLE are oral pellets contained within capsules. Do not swallow the capsules. Do not chew or crush the oral pellets. ENTRESTO SPRINKLE can also be substituted in patients unable to swallow tablets. Use the entire contents of the capsules n capsules. Do not swallow the capsules. Do not chew or crush the oral pellets. ENTRESTO SPRINKLE can also be substituted in patients unable to swallow tablets. Use the entire contents of the capsules to achieve the dose. To administer ENTRESTO oral pellets, open the capsule and sprinkle the full content onto 1 to 2 teaspoons of soft food. Consume the food containing the oral pellets immediately after adding them. Empty capsule shells must be discarded after use and not swallowed. Do not administer ENTRESTO oral pellets via nasogastric, gastrostomy, or other enteral tubes because it may cause obstruction of enteral tubes. 2.6 Dose Adjustment for Patients Not Taking an ACE inhibitor or ARB or Previously Taking Low Doses of These Agents In patients not currently taking an ACE inhibitor or an angiotensin II receptor blocker (ARB) and for patients previously taking low doses of these agents, start ENTRESTO at half the usually recommended starting dose. After initiation, increase the dose every 2 to 4 weeks in adults and every 2 weeks in pediatric patients to follow the recommended dose escalation thereafter [see Dosage and Administration (2.2, 2.3)] . Note: Initiate pediatric patients very 2 to 4 weeks in adults and every 2 weeks in pediatric patients to follow the recommended dose escalation thereafter [see Dosage and Administration (2.2, 2.3)] . Note: Initiate pediatric patients weighing 40 to 50 kg who meet this criterion at 0.8 mg/kg twice daily using the oral suspension or oral pellets [see Dosage and Administration (2.3, 2.4, 2.5)] . 2.7 Dose Adjustment for Severe Renal Impairment In adults and pediatric patients with severe renal impairment estimated glomerular filtration rate (eGFR less than 30 mL/min/1.73 m 2 ), start ENTRESTO at half the usually recommended starting dose. After initiation, increase the dose to follow the recommended dose escalation thereafter [see Dosage and Administration (2.2, 2.3)] . Note: Initiate pediatric patients weighing 40 to 50 kg who meet this criterion at 0.8 mg/kg twice daily using the oral suspension or oral pellets [see Dosage and Administration (2.3, 2.4, 2.5)] . No starting dose adjustment is needed for mild or moderate renal impairment. 2.8 Dose Adjustment for Hepatic Impairment In adults and pediatric patients with moderate hepatic impairment (Child-Pugh B classification), start ENTRESTO at half the usually recommend nal impairment. 2.8 Dose Adjustment for Hepatic Impairment In adults and pediatric patients with moderate hepatic impairment (Child-Pugh B classification), start ENTRESTO at half the usually recommended starting dose. After initiation, increase the dose to follow the recommended dose escalation thereafter [see Dosage and Administration (2.2, 2.3)] . Note: Initiate pediatric patients weighing 40 to 50 kg who meet this criterion at 0.8 mg/kg twice daily using the oral suspension or oral pellets [see Dosage and Administration (2.3, 2.4, 2.5)] . No starting dose adjustment is needed for mild hepatic impairment. Use in patients with severe hepatic impairment is not recommended. 6 ADVERSE REACTIONS Clinically significant adverse reactions that appear in other sections of the labeling include: Angioedema [see Warnings and Precautions (5.2)] Hypotension [see Warnings and Precautions (5.3)] Impaired Renal Function [see Warnings and Precautions (5.4)] Hyperkalemia [see Warnings and Precautions (5.5)] Adverse reactions occurring greater than or equal to 5% are hypotension, hyperkalemia, cough, dizziness, and renal failure. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Novartis Pharma 5.5)] Adverse reactions occurring greater than or equal to 5% are hypotension, hyperkalemia, cough, dizziness, and renal failure. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Novartis Pharmaceuticals Corporation at 1-888-669-6682 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience 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. A total of 6,622 heart failure patients were treated with ENTRESTO in the PARADIGM-HF (vs. enalapril) and PARAGON-HF (vs. valsartan) clinical trials. Of these, 5,085 were exposed for at least 1 year. Adult Heart Failure In PARADIGM-HF, patients were required to complete sequential enalapril and ENTRESTO run-in periods of (median) 15 and 29 days, respectively, prior to entering the randomized double-blind period comparing ENTRESTO and enalapril. During the enalapril run-in period, 1,102 patients (10.5%) were permanently discontinued from the study, 5.6% because of an adverse event, most commonly renal dysfun comparing ENTRESTO and enalapril. During the enalapril run-in period, 1,102 patients (10.5%) were permanently discontinued from the study, 5.6% because of an adverse event, most commonly renal dysfunction (1.7%), hyperkalemia (1.7%) and hypotension (1.4%). During the ENTRESTO run-in period, an additional 10.4% of patients permanently discontinued treatment, 5.9% because of an adverse event, most commonly renal dysfunction (1.8%), hypotension (1.7%) and hyperkalemia (1.3%). Because of this run-in design, the adverse reaction rates described below are lower than expected in practice. In the double-blind period, safety was evaluated in 4,203 patients treated with ENTRESTO and 4,229 treated with enalapril. In PARADIGM-HF, patients randomized to ENTRESTO received treatment for up to 4.3 years, with a median duration of exposure of 24 months; 3,271 patients were treated for more than one year. Discontinuation of therapy because of an adverse event during the double-blind period occurred in 450 (10.7%) of ENTRESTO-treated patients and 516 (12.2%) of patients receiving enalapril. Adverse reactions occurring at an incidence of greater than or equal to 5% in patients who were treated with E 450 (10.7%) of ENTRESTO-treated patients and 516 (12.2%) of patients receiving enalapril. Adverse reactions occurring at an incidence of greater than or equal to 5% in patients who were treated with ENTRESTO in the double-blind period of PARADIGM-HF are shown in Table 3. In PARADIGM-HF, the incidence of angioedema was 0.1% in both the enalapril and ENTRESTO run-in periods. In the double-blind period, the incidence of angioedema was higher in patients treated with ENTRESTO than enalapril (0.5% and 0.2%, respectively). The incidence of angioedema in Black patients was 2.4% with ENTRESTO and 0.5% with enalapril [see Warnings and Precautions (5.2)] . Orthostasis was reported in 2.1% of patients treated with ENTRESTO compared to 1.1% of patients treated with enalapril during the double-blind period of PARADIGM-HF. Falls were reported in 1.9% of patients treated with ENTRESTO compared to 1.3% of patients treated with enalapril. Table 3: Adverse Reactions Reported in greater than or equal to 5% of Patients Treated with ENTRESTO in the Double-Blind Period of PARADIGM-HF ENTRESTO (n = 4,203) % Enalapril (n = 4,229) % Hypotension 18 12 Hyperkalemia 12 14 Cough 9 13 Dizziness 6 5 Renal failur 5% of Patients Treated with ENTRESTO in the Double-Blind Period of PARADIGM-HF ENTRESTO (n = 4,203) % Enalapril (n = 4,229) % Hypotension 18 12 Hyperkalemia 12 14 Cough 9 13 Dizziness 6 5 Renal failure/acute renal failure 5 5 In PARAGON-HF, no new adverse reactions were identified. Pediatric Heart Failure The adverse reactions observed in pediatric patients 1 year to less than 18 years old who received treatment with ENTRESTO were consistent with those observed in adult patients. Laboratory Abnormalities Hemoglobin and Hematocrit Decreases in hemoglobin/hematocrit of greater than 20% were observed in approximately 5% of both ENTRESTO- and enalapril-treated patients in the double-blind period in PARADIGM-HF. Decreases in hemoglobin/hematocrit of greater than 20% were observed in approximately 7% of ENTRESTO-treated patients and 9% of valsartan-treated patients in the double-blind period in PARAGON-HF. Serum Creatinine During the double-blind period in PARADIGM-HF, approximately 16% of both ENTRESTO- and enalapril-treated patients had increases in serum creatinine of greater than 50%. During the double-blind period in PARAGON-HF, approximately 17% of ENTRESTO-treated patients and 21% oth ENTRESTO- and enalapril-treated patients had increases in serum creatinine of greater than 50%. During the double-blind period in PARAGON-HF, approximately 17% of ENTRESTO-treated patients and 21% of valsartan-treated patients had increases in serum creatinine of greater than 50%. Serum Potassium During the double-blind period of PARADIGM-HF, approximately 16% of both ENTRESTO- and enalapril-treated patients had potassium concentrations greater than 5.5 mEq/L. During the double-blind period of PARAGON-HF, approximately 18% of ENTRESTO-treated patients and 20% of valsartan-treated patients had potassium concentrations greater than 5.5 mEq/L. 6.2 Postmarketing Experience The following additional adverse reactions have been reported in postmarketing experience. 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. Hypersensitivity including rash, pruritus, and anaphylactic reaction 1 INDICATIONS AND USAGE OXYCONTIN is indicated for the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate. Limitations of Use Because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses, and because of the greater risks of overdose and death with extended-release opioid formulations, reserve OXYCONTIN for use in patients for whom alternative treatment options (e.g., non-opioid analgesics or immediate-release opioids) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain.Because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses, and because of the greater risks of overdose and death with extended-release opioid formulations, reserve OXYCONTIN for use in patients for whom alternative treatment options (e.g., non-opioid analgesics or immediate-release opioids) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain. OXYCONTIN is not indicated as an as-needed (prn) analgesicOXYCONTIN is not indicated as an as-needed fective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain. OXYCONTIN is not indicated as an as-needed (prn) analgesicOXYCONTIN is not indicated as an as-needed (prn) analgesic OXYCONTIN is an opioid agonist product indicated for the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate. ( 1 ) Limitations of Use Because of the risks of addiction, abuse and misuse with opioids, even at recommended doses, and because of the greater risks of overdose and death with extended-release formulations, reserve OXYCONTIN for use in patients for whom alternative treatment options (e.g. non-opioid analgesics or immediate-release opioids) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain. ( 1 ) OXYCONTIN is not indicated as an as-needed (prn) analgesic. ( 1 ) 2 DOSAGE AND ADMINISTRATION OXYCONTIN 60 mg and 80 mg tablets, a single dose greater than 40 mg, or a total daily dose greater than 80 mg are only for use in patients in whom tolerance to an opioid of comparable potency has been established. ( 2.1 80 mg tablets, a single dose greater than 40 mg, or a total daily dose greater than 80 mg are only for use in patients in whom tolerance to an opioid of comparable potency has been established. ( 2.1 ) For opioid-naïve and opioid non-tolerant patients, initiate with 10 mg tablets orally every 12 hours. ( 2.1 ) Do not abruptly discontinue OXYCONTIN in a physically dependent patient. ( 2.4 ) Tablets must be swallowed intact and are not to be cut, broken, chewed, crushed, or dissolved (risk of potentially fatal dose). ( 2.5 , 5.1 ) OXYCONTIN tablets should be taken one tablet at a time, with enough water to ensure complete swallowing immediately after placing in the mouth. ( 2.5 , 5.9 , 17 ) 2.1 Initial Dosing OXYCONTIN should be prescribed only by healthcare professionals who are knowledgeable in the use of potent opioids for the management of chronic pain. OXYCONTIN 60 mg and 80 mg tablets, a single dose greater than 40 mg, or a total daily dose greater than 80 mg are only for use in patients in whom tolerance to an opioid of comparable potency has been established. Patients considered opioid tolerant are those receiving, for one week or longer, at least 60 mg oral morphine/day, 25 tients in whom tolerance to an opioid of comparable potency has been established. Patients considered opioid tolerant are those receiving, for one week or longer, at least 60 mg oral morphine/day, 25 mcg transdermal fentanyl/hour, 30 mg oral oxycodone/day, 8 mg oral hydromorphone/day, 25 mg oral oxymorphone/day, or an equianalgesic dose of another opioid. Initiate the dosing regimen for each patient individually, taking into account the patient's prior analgesic treatment experience, and risk factors for addiction, abuse, and misuse [see Warnings and Precautions ( 5.1 )] . Monitor patients closely for respiratory depression, especially within the first 24-72 hours of initiating therapy with OXYCONTIN [see Warnings and Precautions ( 5.2 )]. OXYCONTIN tablets must be taken whole, one tablet at a time, with enough water to ensure complete swallowing immediately after placing in the mouth [see Patient Counseling Information ( 17 )] . Crushing, chewing, or dissolving OXYCONTIN tablets will result in uncontrolled delivery of oxycodone and can lead to overdose or death [see Warnings and Precautions ( 5.1 )] . Use of OXYCONTIN as the First Opioid Analgesic Initiate treatment with OXYCONTIN result in uncontrolled delivery of oxycodone and can lead to overdose or death [see Warnings and Precautions ( 5.1 )] . Use of OXYCONTIN as the First Opioid Analgesic Initiate treatment with OXYCONTIN with one 10 mg tablet orally every 12 hours. Use of OXYCONTIN in Patients who are not Opioid Tolerant The starting dose for patients who are not opioid tolerant is OXYCONTIN 10 mg orally every 12 hours. Patients who are opioid tolerant are those receiving, for one week or longer, at least 60 mg oral morphine per day, 25 mcg transdermal fentanyl per hour, 30 mg oral oxycodone per day, 8 mg oral hydromorphone per day, 25 mg oral oxymorphone per day, or an equianalgesic dose of another opioid. Use of higher starting doses in patients who are not opioid tolerant may cause fatal respiratory depression. Conversion from other Oral Oxycodone Formulations to OXYCONTIN Patients receiving other oral oxycodone formulations may be converted to OXYCONTIN by administering one-half of the patient's total daily oral oxycodone dose as OXYCONTIN every 12 hours.Patients receiving other oral oxycodone formulations may be converted to OXYCONTIN by administering one-half of the patient's total daily oral ox daily oral oxycodone dose as OXYCONTIN every 12 hours.Patients receiving other oral oxycodone formulations may be converted to OXYCONTIN by administering one-half of the patient's total daily oral oxycodone dose as OXYCONTIN every 12 hours. Conversion from other Opioids to OXYCONTIN Discontinue all other around-the-clock opioid drugs when OXYCONTIN therapy is initiated. There are no established conversion ratios for conversion from other opioids to OXYCONTIN defined by clinical trials. Discontinue all other around-the-clock opioid drugs when OXYCONTIN therapy is initiated and initiate dosing using OXYCONTIN 10 mg orally every 12 hours. It is safer to underestimate a patient’s 24-hour oral oxycodone requirements and provide rescue medication (e.g., immediate-release opioid) than to overestimate the 24-hour oral oxycodone requirements which could result in adverse reactions. While useful tables of opioid equivalents are readily available, there is substantial inter-patient variability in the relative potency of different opioid drugs and products. Conversion from Methadone to OXYCONTIN Close monitoring is of particular importance when converting from methadone to other opioid agonis n the relative potency of different opioid drugs and products. Conversion from Methadone to OXYCONTIN Close monitoring is of particular importance when converting from methadone to other opioid agonists. The ratio between methadone and other opioid agonists may vary widely as a function of previous dose exposure. Methadone has a long half-life and can accumulate in the plasma. Conversion from Transdermal Fentanyl to OXYCONTIN Eighteen hours following the removal of the transdermal fentanyl patch, OXYCONTIN treatment can be initiated. Although there has been no systematic assessment of such conversion, a conservative oxycodone dose, approximately 10 mg every 12 hours of OXYCONTIN, should be initially substituted for each 25 mcg/hr fentanyl transdermal patch. Follow the patient closely during conversion from transdermal fentanyl to OXYCONTIN, as there is limited documented experience with this conversion.Eighteen hours following the removal of the transdermal fentanyl patch, OXYCONTIN treatment can be initiated. Although there has been no systematic assessment of such conversion, a conservative oxycodone dose, approximately 10 mg every 12 hours of OXYCONTIN, should be initially subst eatment can be initiated. Although there has been no systematic assessment of such conversion, a conservative oxycodone dose, approximately 10 mg every 12 hours of OXYCONTIN, should be initially substituted for each 25 mcg/hr fentanyl transdermal patch. Follow the patient closely during conversion from transdermal fentanyl to OXYCONTIN, as there is limited documented experience with this conversion. 2.2 Titration and Maintenance of Therapy Individually titrate OXYCONTIN to a dose that provides adequate analgesia and minimizes adverse reactions. Continually reevaluate patients receiving OXYCONTIN to assess the maintenance of pain control and the relative incidence of adverse reactions, as well as monitoring for the development of addiction, abuse and misuse. Frequent communication is important among the prescriber, other members of the healthcare team, the patient, and the caregiver/family during periods of changing analgesic requirements, including initial titration. During chronic therapy, periodically reassess the continued need for the use of opioid analgesics. Patients who experience breakthrough pain may require a dose increase of OXYCONTIN or may need rescue medication with a rapy, periodically reassess the continued need for the use of opioid analgesics. Patients who experience breakthrough pain may require a dose increase of OXYCONTIN or may need rescue medication with an appropriate dose of an immediate-release analgesic. If the level of pain increases after dose stabilization, attempt to identify the source of increased pain before increasing the OXYCONTIN dose. Because steady-state plasma concentrations are approximated in 1 day, OXYCONTIN dosage may be adjusted every 1 to 2 days. If unacceptable opioid-related adverse reactions are observed, the subsequent dose may be reduced. Adjust the dose to obtain an appropriate balance between management of pain and opioid-related adverse reactions. There are no well-controlled clinical studies evaluating the safety and efficacy with dosing more frequently than every 12 hours. As a guideline, the total daily oxycodone dose usually can be increased by 25% to 50% of the current dose, each time an increase is clinically indicated.There are no well-controlled clinical studies evaluating the safety and efficacy with dosing more frequently than every 12 hours. As a guideline, the total daily oxycodone dose usually cally indicated.There are no well-controlled clinical studies evaluating the safety and efficacy with dosing more frequently than every 12 hours. As a guideline, the total daily oxycodone dose usually can be increased by 25% to 50% of the current dose, each time an increase is clinically indicated. 2.3 Patients with Hepatic Impairment For patients with hepatic impairment, start dosing patients at 1/3 to 1/2 the usual starting dose followed by careful dose titration [see Clinical Pharmacology ( 12.3 )] . 2.4 Discontinuation of OXYCONTIN When the patient no longer requires therapy with OXYCONTIN tablets, use a gradual downward titration of the dose to prevent signs and symptoms of withdrawal in the physically dependent patient. Do not abruptly discontinue OXYCONTIN. 2.5 Administration of OXYCONTIN Instruct patients to swallow OXYCONTIN tablets intact. The tablets are not to be crushed, dissolved, or chewed due to the risk of rapid release and absorption of a potentially fatal dose of oxycodone [see Warnings and Precautions ( 5.1 )] . Instruct patients to take OXYCONTIN one tablet at a time and with enough water to ensure complete swallowing immediately after placing in the mouth [see codone [see Warnings and Precautions ( 5.1 )] . Instruct patients to take OXYCONTIN one tablet at a time and with enough water to ensure complete swallowing immediately after placing in the mouth [see Warnings and Precautions ( 5.9 ) and Patient Counseling Information ( 17 )]. 6 ADVERSE REACTIONS The following serious adverse reactions are described elsewhere in the labeling: Addiction, Abuse, and Misuse [see Warnings and Precautions ( 5.1 )] Life-Threatening Respiratory Depression [see Warnings and Precautions ( 5.2 )] Neonatal Opioid Withdrawal Syndrome [see Warnings and Precautions ( 5.3 )] Interactions with Other CNS Depressants [see Warnings and Precautions ( 5.4 )] Hypotensive Effects [see Warnings and Precautions ( 5.7 )] Gastrointestinal Effects [see Warnings and Precautions ( 5.9 , 5.10 )] Seizures [see Warnings and Precautions ( 5.11 )] Most common adverse reactions (>5%) are constipation, nausea, somnolence, dizziness, vomiting, pruritus, headache, dry mouth, asthenia, and sweating. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Purdue Pharma L.P. at 1-888-726-7535 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trial Experience Because clinical t weating. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Purdue Pharma L.P. at 1-888-726-7535 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trial Experience 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. The safety of OXYCONTIN was evaluated in double-blind clinical trials involving 713 patients with moderate to severe pain of various etiologies. In open-label studies of cancer pain, 187 patients received OXYCONTIN in total daily doses ranging from 20 mg to 640 mg per day. The average total daily dose was approximately 105 mg per day. OXYCONTIN may increase the risk of serious adverse reactions such as those observed with other opioid analgesics, including respiratory depression, apnea, respiratory arrest, circulatory depression, hypotension, or shock [see Overdosage ( 10 )] . The most common adverse reactions (>5%) reported by patients in clinical trials comparing OXYCONTIN with placebo are shown in Table 1 below: TABLE 1: Common Adverse React ock [see Overdosage ( 10 )] . The most common adverse reactions (>5%) reported by patients in clinical trials comparing OXYCONTIN with placebo are shown in Table 1 below: TABLE 1: Common Adverse Reactions (>5%) Adverse Reaction OXYCONTIN (n=227) Placebo (n=45) (%) (%) Constipation (23) (7) Nausea (23) (11) Somnolence (23) (4) Dizziness (13) (9) Pruritus (13) (2) Vomiting (12) (7) Headache (7) (7) Dry Mouth (6) (2) Asthenia (6) - Sweating (5) (2) In clinical trials, the following adverse reactions were reported in patients treated with OXYCONTIN with an incidence between 1% and 5%: Gastrointestinal disorders: abdominal pain, diarrhea, dyspepsia, gastritis General disorders and administration site conditions: chills, fever Metabolism and nutrition disorders: anorexia Musculoskeletal and connective tissue disorders: twitching Psychiatric disorders: abnormal dreams, anxiety, confusion, dysphoria, euphoria, insomnia, nervousness, thought abnormalities Respiratory, thoracic and mediastinal disorders: dyspnea, hiccups Skin and subcutaneous tissue disorders: rash Vascular disorders: postural hypotension The following adverse reactions occurred in less than 1% of patients involved in clinic isorders: dyspnea, hiccups Skin and subcutaneous tissue disorders: rash Vascular disorders: postural hypotension The following adverse reactions occurred in less than 1% of patients involved in clinical trials: Blood and lymphatic system disorders: lymphadenopathy Ear and labyrinth disorders: tinnitus Eye disorders: abnormal vision Gastrointestinal disorders: dysphagia, eructation, flatulence, gastrointestinal disorder, increased appetite, stomatitis General disorders and administration site conditions: withdrawal syndrome (with and without seizures), edema, peripheral edema, thirst, malaise, chest pain, facial edema Injury, poisoning and procedural complications: accidental injury Investigations: ST depression Metabolism and nutrition disorders: dehydration Nervous system disorders: syncope, migraine, abnormal gait, amnesia, hyperkinesia, hypesthesia, hypotonia, paresthesia, speech disorder, stupor, tremor, vertigo, taste perversion Psychiatric disorders: depression, agitation, depersonalization, emotional lability, hallucination Renal and urinary disorders: dysuria, hematuria, polyuria, urinary retention Reproductive system and breast disorders: impotence Respiratory, thoracic an onalization, emotional lability, hallucination Renal and urinary disorders: dysuria, hematuria, polyuria, urinary retention Reproductive system and breast disorders: impotence Respiratory, thoracic and mediastinal disorders: cough increased, voice alteration Skin and subcutaneous tissue disorders: dry skin, exfoliative dermatitis 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of controlled-release oxycodone: abuse, addiction, amenorrhea, cholestasis, death, dental caries, increased hepatic enzymes, hyperalgesia, hypogonadism, hyponatremia, ileus, muscular hypertonia, overdose, palpitations (in the context of withdrawal), seizures, syndrome of inappropriate antidiuretic hormone secretion, and urticaria. Anaphylaxis has been reported with ingredients contained in OXYCONTIN. Advise patients how to recognize such a reaction and when to seek medical attention. In addition to the events listed above, the following have also been reported, potentially due to the swelling and hydrogelling property of the tablet: choking, gagging, regurgitation, tablets stuck in the throat and difficulty swallowing the tablet. Uses First aid to help prevent the risk of bacterial contamination in cuts, scrapes, burns, lacerations and skin infections. Purpose First aid antiseptic Warnings For external use only. When using this product avoid contact with eyes. In case of eye contact flush eyes with water . Stop use and ask a doctor if irritation or redness develops, or if condition persists for more than 72 hours Directions For ages two years and older. Spray a small amount on the area up to 3 times a day. Wipe off excess with sterile Gauze. Once dry, may be covered with a bandage Keep out of reach of children. If swallowed, get medical help or contact a Poison Control Center right away. 1 INDICATIONS AND USAGE Sodium Iodide I 131 Capsules Therapeutic is indicated for the treatment of hyperthyroidism and thyroid carcinomas that take up iodide. Palliative effects may be observed in patients with advanced thyroid malignancy if the metastatic lesions take up iodide. Sodium Iodide I 131 Capsules Therapeutic is a radioactive therapeutic agent indicated for the treatment of hyperthyroidism and thyroid carcinomas that take up iodine. Palliative effects may be observed in patients with advanced thyroid malignancy if the metastatic lesions take up iodine. ( 1 ) 2 DOSAGE AND ADMINISTRATION Use safe handling measures to minimize inadvertent radiation exposure. ( 2.1 ) Hyperthyroidism 148 to 370 megabecquerels (MBq) (4 to 10 millicuries, mCi). Toxic nodular goiter and other situations may require larger doses. ( 2.2 ) Thyroid Carcinoma For thyroid carcinoma, 3700 to 5550 MBq (100 to 150 mCi). ( 2.3 ) For post-operative ablation of normal thyroid tissue: 1850 MBq (50 mCi). ( 2.3 ) Individualize therapy, including dose selection, based upon patient-specific factors detected during the therapeutic planning process. ( 2.4 ) 2.1 Radiation Safety Sodium iodide I-131 capsules emit ra Individualize therapy, including dose selection, based upon patient-specific factors detected during the therapeutic planning process. ( 2.4 ) 2.1 Radiation Safety Sodium iodide I-131 capsules emit radiation and must be handled with safety measures to minimize inadvertent radiation exposure to clinical personnel and patients [see Warnings and Precautions ( 5.7 )] . Radiopharmaceuticals should be used only by or under the direction of phy­sicians who are qualified by training and experience in the safe use and handling of radionuclides and whose experience and training have been approved by the appropriate governmental agency authorized to license the use of radionuclides. Wear waterproof gloves during the entire sodium iodide I-131 capsule handling and administration procedure. Maintain adequate shielding during the radiation-emitting life of the product. Measure the patient dose using a suitable radioactivity calibration system immediately prior to administration. 2.2 Hyperthyroidism For hyperthyroidism, the usual sodium iodide I-131 dose range is 148 to 370 MBq (4 to 10 mCi). Higher doses may be necessary for the treatment of toxic nodular goiter and other special situations. Con For hyperthyroidism, the usual sodium iodide I-131 dose range is 148 to 370 MBq (4 to 10 mCi). Higher doses may be necessary for the treatment of toxic nodular goiter and other special situations. Consider discontinuation of anti-thyroid therapy in a severely hyperthyroid pa­tient three to four days before administration of sodium iodide I-131. Evaluate patients for risk of thyroid enlargement and obstruction of structures in the neck [see Warnings and Precautions ( 5.1 , 5.2 )] . 2.3 Thyroid Carcinoma For thyroid carcinoma, the usual sodium iodide I-131 therapeutic dose is 3700 to 5550 MBq (100 to 150 mCi). For ablation of post-operative residual thyroid tissue, the usual dose is 1850 MBq (50 mCi). 2.4 Individualization of Therapy Individualize sodium iodide I-131 therapy, including dose selection, based upon patient-specific factors such as the nature of the underlying condition, co-morbidities, age, estimated thyroid tissue iodine uptake, thyroid size, as well as ability of the patient to comply with the therapeutic regimen and radiation safety procedures. Perform a clinical assessment, including history, physical examination and laboratory testing when preparing patients for so ent to comply with the therapeutic regimen and radiation safety procedures. Perform a clinical assessment, including history, physical examination and laboratory testing when preparing patients for sodium iodide I-131 therapy in order to detect conditions which may alter thyroid iodine uptake and increase the risks of the therapy or diminish its effectiveness. For example, intake of iodine in radiographic contrast may diminish thyroid iodine uptake while low serum chloride or nephrosis may increase thyroid iodine uptake. Obtain a drug history and ascertain whether any medications need to be withheld before the administration of the therapy [see Drug Interactions ( 7 )] . 2.5 Radiation Dosimetry The estimated absorbed radiation doses 1 to an average (70 kg) euthyroid (normal functioning thy­roid) patient from an oral dose of iodine-131 in both milligray (mGy) per megabecquerel (MBq) and rad per millicurie (mCi) are shown in Table 1. Table 1. Absorbed Radiation Doses Tissue Thyroid Uptake 5% 15% 25% mGy/ MBq rads/ mCi mGy/ MBq rads/ mCi mGy/ MBq rads/ mCi Thyroid 72 266 210 777 360 1300 Stomach Wall 0.45 1.7 0.46 1.7 0.46 1.7 Red Marrow 0.038 0.14 0.054 0.20 0.07 0.26 Liver 0.03 0.11 e 5% 15% 25% mGy/ MBq rads/ mCi mGy/ MBq rads/ mCi mGy/ MBq rads/ mCi Thyroid 72 266 210 777 360 1300 Stomach Wall 0.45 1.7 0.46 1.7 0.46 1.7 Red Marrow 0.038 0.14 0.054 0.20 0.07 0.26 Liver 0.03 0.11 0.032 0.12 0.035 0.13 Testes 0.029 0.11 0.028 0.10 0.027 0.10 Ovaries 0.044 0.16 0.043 0.16 0.043 0.16 Urinary Bladder 0.58 2.1 0.52 1.9 0.46 1.7 Salivary Glands 2 0.5 1.85 0.5 1.85 0.5 1.85 Other 0.040 0.15 0.065 0.24 0.090 0.33 2.1 Radiation Safety Sodium iodide I-131 capsules emit radiation and must be handled with safety measures to minimize inadvertent radiation exposure to clinical personnel and patients [see Warnings and Precautions ( 5.7 )] . Radiopharmaceuticals should be used only by or under the direction of phy­sicians who are qualified by training and experience in the safe use and handling of radionuclides and whose experience and training have been approved by the appropriate governmental agency authorized to license the use of radionuclides. Wear waterproof gloves during the entire sodium iodide I-131 capsule handling and administration procedure. Maintain adequate shielding during the radiation-emitting life of the product. Measure the patient dose using a suitable ra he entire sodium iodide I-131 capsule handling and administration procedure. Maintain adequate shielding during the radiation-emitting life of the product. Measure the patient dose using a suitable radioactivity calibration system immediately prior to administration. 2.2 Hyperthyroidism For hyperthyroidism, the usual sodium iodide I-131 dose range is 148 to 370 MBq (4 to 10 mCi). Higher doses may be necessary for the treatment of toxic nodular goiter and other special situations. Consider discontinuation of anti-thyroid therapy in a severely hyperthyroid pa­tient three to four days before administration of sodium iodide I-131. Evaluate patients for risk of thyroid enlargement and obstruction of structures in the neck [see Warnings and Precautions ( 5.1 , 5.2 )] . 2.3 Thyroid Carcinoma For thyroid carcinoma, the usual sodium iodide I-131 therapeutic dose is 3700 to 5550 MBq (100 to 150 mCi). For ablation of post-operative residual thyroid tissue, the usual dose is 1850 MBq (50 mCi). 2.4 Individualization of Therapy Individualize sodium iodide I-131 therapy, including dose selection, based upon patient-specific factors such as the nature of the underlying condition, co-morbidities, a Individualization of Therapy Individualize sodium iodide I-131 therapy, including dose selection, based upon patient-specific factors such as the nature of the underlying condition, co-morbidities, age, estimated thyroid tissue iodine uptake, thyroid size, as well as ability of the patient to comply with the therapeutic regimen and radiation safety procedures. Perform a clinical assessment, including history, physical examination and laboratory testing when preparing patients for sodium iodide I-131 therapy in order to detect conditions which may alter thyroid iodine uptake and increase the risks of the therapy or diminish its effectiveness. For example, intake of iodine in radiographic contrast may diminish thyroid iodine uptake while low serum chloride or nephrosis may increase thyroid iodine uptake. Obtain a drug history and ascertain whether any medications need to be withheld before the administration of the therapy [see Drug Interactions ( 7 )] . 2.5 Radiation Dosimetry The estimated absorbed radiation doses 1 to an average (70 kg) euthyroid (normal functioning thy­roid) patient from an oral dose of iodine-131 in both milligray (mGy) per megabecquerel (MBq) and rad per milli mated absorbed radiation doses 1 to an average (70 kg) euthyroid (normal functioning thy­roid) patient from an oral dose of iodine-131 in both milligray (mGy) per megabecquerel (MBq) and rad per millicurie (mCi) are shown in Table 1. Table 1. Absorbed Radiation Doses Tissue Thyroid Uptake 5% 15% 25% mGy/ MBq rads/ mCi mGy/ MBq rads/ mCi mGy/ MBq rads/ mCi Thyroid 72 266 210 777 360 1300 Stomach Wall 0.45 1.7 0.46 1.7 0.46 1.7 Red Marrow 0.038 0.14 0.054 0.20 0.07 0.26 Liver 0.03 0.11 0.032 0.12 0.035 0.13 Testes 0.029 0.11 0.028 0.10 0.027 0.10 Ovaries 0.044 0.16 0.043 0.16 0.043 0.16 Urinary Bladder 0.58 2.1 0.52 1.9 0.46 1.7 Salivary Glands 2 0.5 1.85 0.5 1.85 0.5 1.85 Other 0.040 0.15 0.065 0.24 0.090 0.33 6 ADVERSE REACTIONS The following serious adverse reactions are described below and elsewhere in labeling: Radiation-induced Thyroiditis [see Warnings and Precautions ( 5.1 )] Thyroid-stimulating Hormone and Thyroid Enlargement [see Warnings and Precautions ( 5.2 )] Radiation-induced Toxicities [see Warnings and Precautions ( 5.3 )] Hypersensitivity Reactions [see Warnings and Precautions ( 5.4 )] Fetal Risk [see Warnings and Precautions ( 5.5 )] Transient Infertility [see War ced Toxicities [see Warnings and Precautions ( 5.3 )] Hypersensitivity Reactions [see Warnings and Precautions ( 5.4 )] Fetal Risk [see Warnings and Precautions ( 5.5 )] Transient Infertility [see Warnings and Precautions ( 5.6 )] Radiation Exposure to Other Individuals [see Warnings and Precautions ( 5.7 )] Radiation-related adverse reactions are a function of the dose level received by the patient. The following adverse reactions have been reported with doses of sodium iodide I-131 used in the treatment of benign disease, such as hyperthyroidism: Gastrointestinal disorders: sialadenitis Cardiac disorders: chest pain and tachycardia Skin and subcutaneous tissue disorders: iododerma, itching skin, rash, and hives Endocrine disorders: hypothyroidism, hyperthyroidism, thyrotoxic crisis, hypoparathyroidism General disorders and administration site conditions: local swelling The following adverse reactions have been reported with doses of sodium iodide I-131 used in the treatment of malignant disease: Blood and lymphatic system disorders including fatalities: radiation sickness, bone marrow depression, anemia, leucopenia, thrombocytopenia, and blood dyscrasia Neoplasms benign, malignan ant disease: Blood and lymphatic system disorders including fatalities: radiation sickness, bone marrow depression, anemia, leucopenia, thrombocytopenia, and blood dyscrasia Neoplasms benign, malignant and unspecified (including cysts and polyps): leukemia and solid cancers Eye disorders: lacrimal gland dysfunction Gastrointestinal disorders: salivary gland dysfunction, nausea, vomiting Congenital, familial and genetic disorders: congenital hypothyroidism and chromosomal abnormalities Adverse reactions that occur after treatment of benign disease may also occur after treatment of malignant disease. Tenderness, pain on swallowing, sore throat, and cough have been reported, generally around the third day after sodium iodide I-131 administration. Adverse reactions that have been reported with doses of sodium iodide I-131 used in the treatment of benign disease include sialadenitis, chest pain, tachycardia, iododerma, itching skin, rash, hives, hypothyroidism, hyperthyroidism, thyrotoxic crisis, hypoparathyroidism, and local swelling. ( 6 ) Adverse reactions that have been reported with doses of sodium iodide I-131 used in the treatment of malignant disease include radiation sickness, risis, hypoparathyroidism, and local swelling. ( 6 ) Adverse reactions that have been reported with doses of sodium iodide I-131 used in the treatment of malignant disease include radiation sickness, bone marrow depression, anemia, leucopenia, thrombocytopenia, blood dyscrasia, leukemia, solid cancers, lacrimal gland dysfunction, salivary gland dysfunction, congenital hypothyroidism, and chromosomal abnormalities. ( 6 ) To report SUSPECTED ADVERSE REACTIONS contact Mallinckrodt Inc. at 1-888-744-1414 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch Uses • temporarily relieves cough due to minor throat and bronchial irritation associates with a cold • temporarily relieves minor aches and pains of muscles and joints Purpose Camphor - cough suppressant/topical analgesic Eucalyptus oil - cough suppressant Menthol - Cough suppressant/topical analgesic Warnings For external use only Ask a doctor before use if you have • cough that occurs with too much phlegm (mucus) • chronic cough that lasts or as occurs with smoking, asthma, or emphysema When using this product • do not heat • do not microwave • do not add to hot water or any container where heating water. May cause splattering and result in burns. • do not take by mouth or place in nostrils • do not get into eyes • do not bandage tightly • do not apply to wounds or damaged skin Stop use and ask a doctor if • cough lasts more than 7 days, comes back, or occurs with fever, rash, or headache that lasts. These could be signs of a serious condition. • muscles aches and pains worsen, persist for more than 7 days, or clear up and occur again within a few days If pregnant or breast-feeding ask a health professional before use. Keep Out of Reach of Children In case of accidental ingestio ist for more than 7 days, or clear up and occur again within a few days If pregnant or breast-feeding ask a health professional before use. Keep Out of Reach of Children In case of accidental ingestion, get medical help or contact a Poison Control Center right away. Directions • see important warnings under "When using this product" • adults and children 2 years and over: • rub a thick layer on chest & throat, or rub on sore aching muscles • cover with warm, dry cloth if desired • keep clothing loose about the throat/chest to help vapors reach the nose/mouth • repeat up to three times per 24 hours, or as directed by a doctor • children under 2 years: ask a doctor Ask a doctor before use if you have • cough that occurs with too much phlegm (mucus) • chronic cough that lasts or as occurs with smoking, asthma, or emphysema Stop use and ask a doctor if • cough lasts more than 7 days, comes back, or occurs with fever, rash, or headache that lasts. These could be signs of a serious condition. • muscles aches and pains worsen, persist for more than 7 days, or clear up and occur again within a few days Keep Out of Reach of Children In case of accidental ingestion, get medical help or conta . • muscles aches and pains worsen, persist for more than 7 days, or clear up and occur again within a few days Keep Out of Reach of Children In case of accidental ingestion, get medical help or contact a Poison Control Center right away. Use reduces underarm wetness Purpose Antiperspirant Warnings For external use only. Do not use on broken skin Ask a doctor before use if you have kidney disease Stop use if rash or irritation occurs Keep out of reach of children. If swallowed, get medical help or contact a Poison Control Center right away. Directions apply to underarms only Ask a doctor before use if you have kidney disease Stop use if rash or irritation occurs Keep out of reach of children. If swallowed, get medical help or contact a Poison Control Center right away. Indications: Temporarily relieves minor burns, dry, chapped, fissured and macerated skin and lips, also relieves Psoriais, Eczema, mild sunburn, abrasions and contusions, diaper dermatitis, hemorrhoids, and prickly heat. Purpose Petrolatum USP 58.95% .................................. Protectant Anhydrous Lanolin USP 35% ....................... Protectant Warnings: For external use only. Discontinue use if signs of irritation appear. If condition worsens consult a doctor. Do not use over deep, infected, or puncture wounds. Directions: Apply a thin film to clean, dry skin three times daily. May be covered with sterile gauze, if desired. Keep from children. Indications Indications: To be used for acute self-limiting conditions according to standard homeopathic indications Purpose Purpose: Hoarse cough Warning If pregnant or nursing, consult a practitioner before using. Directions Take at onset of symptoms. Repeat every 2 hours or as needed until relieved. If condition persists or worsens discontinue use and consult a practitioner. Adults: dissolve 5-10 pellets in 1 oz. of filtered water or take dry by mouth. Children and infants: 1-5 pellets. Keep Out of Reach of Children Keep these and all medications out of the reach of children. INDICATIONS AND USAGE Oxycodone and acetaminophen tablets USP are indicated for the relief of moderate to moderately severe pain. WARNINGS DOSAGE AND ADMINISTRATION Dosage should be adjusted according to the severity of the pain and the response of the patient. It may occasionally be necessary to exceed the usual dosage recommended below in cases of more severe pain or in those patients who have become tolerant to the analgesic effect of opioids. If pain is constant, the opioid analgesic should be given at regular intervals on an around-the-clock schedule. Oxycodone and acetaminophen tablets are given orally. The total daily dose of acetaminophen should not exceed 4 grams. Strength Usual Adult Dosage Maximal Daily Dose Oxycodone and acetaminophen tablets 5 mg/325 mg 1 tablet every 6 hours as needed for pain 12 Tablets Oxycodone and acetaminophen tablets 7.5 mg/325 mg 1 tablet every 6 hours as needed for pain 8 Tablets Oxycodone and acetaminophen tablets 7.5 mg/500 mg 1 tablet every 6 hours as needed for pain 8 Tablets Oxycodone and acetaminophen tablets 10 mg/325 mg 1 tablet every 6 hours as needed for pain 6 Tablets ADVERSE REACTIONS Serious adverse reactions that may be associate ours as needed for pain 8 Tablets Oxycodone and acetaminophen tablets 10 mg/325 mg 1 tablet every 6 hours as needed for pain 6 Tablets ADVERSE REACTIONS Serious adverse reactions that may be associated with oxycodone and acetaminophen tablet use include respiratory depression, apnea, respiratory arrest, circulatory depression, hypotension, and shock ( see OVERDOSAGE ). The most frequently observed non-serious adverse reactions include lightheadedness, dizziness, drowsiness or sedation, nausea, and vomiting. These effects seem to be more prominent in ambulatory than in nonambulatory patients, and some of these adverse reactions may be alleviated if the patient lies down. Other adverse reactions include euphoria, dysphoria, constipation, and pruritus. Hypersensitivity reactions may include: Skin eruptions, urticarial, erythematous skin reactions. Hematologic reactions may include: Thrombocytopenia, neutropenia, pancytopenia, hemolytic anemia. Rare cases of agranulocytosis have likewise been associated with acetaminophen use. In high doses, the most serious adverse effect is a dose-dependent, potentially fatal hepatic necrosis. Renal tubular necrosis and hypoglycemic coma also may occ een associated with acetaminophen use. In high doses, the most serious adverse effect is a dose-dependent, potentially fatal hepatic necrosis. Renal tubular necrosis and hypoglycemic coma also may occur. Other adverse reactions obtained from postmarketing experiences with oxycodone and acetaminophen tablets are listed by organ system and in decreasing order of severity and/or frequency as follows: Body as a Whole Anaphylactoid reaction, allergic reaction, malaise, asthenia, fatigue, chest pain, fever, hypothermia, thirst, headache, increased sweating, accidental overdose, non-accidental overdose Cardiovascular Hypotension, hypertension, tachycardia, orthostatic hypotension, bradycardia, palpitations, dysrhythmias Central and Peripheral Nervous System Stupor, tremor, paraesthesia, hypoaesthesia, lethargy, seizures, anxiety, mental impairment, agitation, cerebral edema, confusion, dizziness Fluid and Electrolyte Dehydration, hyperkalemia, metabolic acidosis, respiratory alkalosis Gastrointestinal Dyspepsia, taste disturbances, abdominal pain, abdominal distention, sweating increased, diarrhea, dry mouth, flatulence, gastro-intestinal disorder, nausea, vomiting, pancreatitis, intestin ntestinal Dyspepsia, taste disturbances, abdominal pain, abdominal distention, sweating increased, diarrhea, dry mouth, flatulence, gastro-intestinal disorder, nausea, vomiting, pancreatitis, intestinal obstruction, ileus Hepatic Transient elevations of hepatic enzymes, increase in bilirubin, hepatitis, hepatic failure, jaundice, hepatotoxicity, hepatic disorder Hearing and Vestibular Hearing loss, tinnitus Hematologic Thrombocytopenia Hypersensitivity Acute anaphylaxis, angioedema, asthma, bronchospasm, laryngeal edema, urticaria, anaphylactoid reaction Metabolic and Nutritional Hypoglycemia, hyperglycemia, acidosis, alkalosis Musculoskeletal Myalgia, rhabdomyolysis Ocular Miosis, visual disturbances, red eye Psychiatric Drug dependence, drug abuse, insomnia, confusion, anxiety, agitation, depressed level of consciousness, nervousness, hallucination, somnolence, depression, suicide Respiratory System Bronchospasm, dyspnea, hyperpnea, pulmonary edema, tachypnea, aspiration, hypoventilation, laryngeal edema Skin and Appendages Erythema, urticaria, rash, flushing Urogenital Interstitial nephritis, papillary necrosis, proteinuria, renal insufficiency and failure, urinary retention Use For the temporary relief of pain Purpose Topical Anesthetic Warnings For external use only. Avoid contact with eyes. Not for prolonged use. Do not use in large quantities, particularly over raw surfaces or blistered areas. Directions Adults and children 2 years old and older Clean the affected area Apply to affected area not more than 3 to 4 times daily Remove residue if desired Children under 2 years old: Consult a doctor Stop Use and Ask a Doctor if the condition worsens ■ symptoms persist for more than seven days or clear up and occur again within a few days. Rash or irritation develops, persists, or increases. If pregnant or breastfeeding, ask a health professional before use. Keep out of reach of children. If swallowed, get medical help, or contact a Poison Control Center right away +1 800-222-1222 HOMEOPATHIC INDICATIONS: For temporary relief of symptoms related to attention deficit including hyperactivity and poor concentration.** **These statements are based upon traditional homeopathic principles. They have not been reviewed by the Food and Drug Administration. HOMEOPATHIC INDICATIONS: For temporary relief of symptoms related to attention deficit including hyperactivity and poor concentration.** **These statements are based upon traditional homeopathic principles. They have not been reviewed by the Food and Drug Administration. WARNINGS: Keep out of reach of children. In case of overdose, contact physician or a Poison Control Center right away. If pregnant or breast-feeding, ask a health professional before use. Tamper seal: "Sealed for Your Protection." Do not use if seal is broken or missing. DIRECTIONS: 1-10 drops under the tongue, 3 times a day or as directed by a health professional. Consult a physician for use in children under 12 years of age. KEEP OUT OF REACH OF CHILDREN: Keep out of reach of children. In case of overdose, contact physician or a Poison Control Center right away. INDICATIONS AND USAGE Carefully consider the potential benefits and risks of etodolac tablets and other treatment options before deciding to use etodolac tablets. Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals (see WARNINGS ). Etodolac tablets are indicated: For acute and long-term use in the management of signs and symptoms of the following: Osteoarthritis Rheumatoid arthritis For the management of acute pain 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, including myocardial infarction (MI) and stroke, which can be fatal. Based on available data, it is unclear that the risk for CV thrombotic events is similar for all NSAIDs. The relative increase in serious CV thrombotic events over baseline conferred by NSAID use appears to be similar in those with and without known CV disease or risk factors for CV disease. However, patients with known CV disease or risk factors had a higher absolute incidence of excess serious CV thrombotic eve r in those with and without known CV disease or risk factors for CV disease. However, patients with known CV disease or risk factors had a higher absolute incidence of excess serious CV thrombotic events, due to their increased baseline rate. Some observational studies found that this increased risk of serious CV thrombotic events began as early as the first weeks of treatment. The increase in CV thrombotic risk has been observed most consistently at higher doses. To minimize the potential risk for an adverse CV event in NSAID-treated patients, use the lowest effective dose for the shortest duration possible. Physicians and patients should remain alert for the development of such events, throughout the entire treatment course, even in the absence of previous CV symptoms. Patients should be informed about the symptoms of serious CV events and the steps to take if they occur. There is no 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, such as etodolac, increases the risk of serious gastrointestinal (GI) events (see WARNINGS ). Status Post Coronary Art tic events associated with NSAID use. The concurrent use of aspirin and an NSAID, such as etodolac, increases the risk of serious gastrointestinal (GI) events (see WARNINGS ). Status Post Coronary Artery Bypass Graft (CABG) Surgery Two large, controlled clinical trials of a COX-2 selective NSAID for the treatment of pain in the first 10 to 14 days following CABG surgery found an increased incidence of myocardial infarction and stroke. NSAIDs are contraindicated in the setting of CABG (see CONTRAINDICATIONS ). Post-MI Patients Observational studies conducted in the Danish National Registry have demonstrated that patients treated with NSAIDs in the post-MI period were at increased risk of reinfarction, CV-related death, and all-cause mortality beginning in the first week of treatment. In this same cohort, the incidence of death in the first year post MI was 20 per 100 person years in NSAID-treated patients compared to 12 per 100 person years in non-NSAID exposed patients. Although the absolute rate of death declined somewhat after the first year post-MI, the increased relative risk of death in NSAID users persisted over at least the next four years of follow-up. Avoid the use of etod solute rate of death declined somewhat after the first year post-MI, the increased relative risk of death in NSAID users persisted over at least the next four years of follow-up. Avoid the use of etodolac in patients with a recent MI unless the benefits are expected to outweigh the risk of recurrent CV thrombotic events. If etodolac is used in patients with a recent MI, monitor patients for signs of cardiac ischemia. Hypertension NSAIDs, including etodolac, 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 etodolac, 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. Heart Failure and Edema The Coxib and traditional NSAID Trialists' Collaboration meta-analysis of randomized controlled trials demonstrated an approximately two-fold increase in hospitalizations for heart failure in COX-2 selective-treated patients and nonselec ists' Collaboration meta-analysis of randomized controlled trials demonstrated an approximately two-fold increase in hospitalizations for heart failure in COX-2 selective-treated patients and nonselective NSAID-treated patients compared to placebo-treated patients. In a Danish National Registry study of patients with heart failure, NSAID use increased the risk of MI, hospitalization for heart failure, and death. Additionally, fluid retention and edema have been observed in some patients treated with NSAIDs. Use of etodolac may blunt the CV effects of several therapeutic agents used to treat these medical conditions [e.g., diuretics, ACE inhibitors, or angiotensin receptor blockers (ARBs)] (see DRUG INTERACTIONS ). Avoid the use of etodolac in patients with severe heart failure unless the benefits are expected to outweigh the risk of worsening heart failure. If etodolac is used in patients with severe heart failure, monitor patients for signs of worsening heart failure. Gastrointestinal Effects - Risk of Ulceration, Bleeding, and Perforation NSAIDs, including etodolac, can cause serious gastrointestinal (GI) adverse events including inflammation, bleeding, ulceration, and perforatio Effects - Risk of Ulceration, Bleeding, and Perforation NSAIDs, including etodolac, 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 to 6 months, and in about 2 to 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. Physicians should inform patients about the signs and/or symptoms of serious GI toxicity and what steps to take if they occur. 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, a ke if they occur. 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 , and who use NSAIDs have a greater than 10-fold increased risk for developing a GI bleed compared to patients with neither of these risk factors. Other factors that increase the risk for 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 ulceration and bleeding during NSAID therapy and promptly initiate additional evaluation and treatment if a serious GI adverse event is suspected. This should include dis for signs and symptoms of GI ulceration and bleeding during NSAID therapy and promptly initiate additional evaluation and treatment if a serious GI adverse 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 nonsteroidal anti-inflammatory drug may cause a dose-dependent reduction in prostaglandin formation and, secondarily, in renal blood flow, which may precipitate overt renal decompensation. Patients at greater 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. Renal pelvic transitional epithelial hyperplasia, a spontaneous change occurring with tors, and the elderly. Discontinuation of NSAID therapy is usually followed by recovery to the pretreatment state. Renal pelvic transitional epithelial hyperplasia, a spontaneous change occurring with variable frequency, was observed with increased frequency in treated male rats in a 2-year chronic study. Caution is recommended in patients with pre-existing kidney disease. Advanced Renal Disease No information is available from controlled clinical studies regarding the use of etodolac, in patients with advanced renal disease. Therefore, treatment with etodolac is not recommended in these patients with advanced renal disease. If etodolac therapy must be initiated, close monitoring of the patient's renal function is advisable. Anaphylactoid Reactions As with other NSAIDs, anaphylactoid reactions may occur in patients without prior exposure to etodolac. Etodolac 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. Fatal reactions have been reported in such patients (see CONTRAIND ce rhinitis with or without nasal polyps, or who exhibit severe, potentially fatal bronchospasm after taking aspirin or other NSAIDs. Fatal reactions have been reported in such patients (see CONTRAINDICATIONS and PRECAUTIONS, General, Pre-existing Asthma ). Emergency help should be sought in cases where an anaphylactoid reaction occurs. Skin Reactions NSAIDs, including etodolac, 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. Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) has been reported in patients taking NSAIDs such as etodolac. Some of these events have been fatal or life-threatening. DRESS typically, although not exclusively, presents with fever, rash, lymphadenopathy, and/or facial swelling. Other clinical manifestations may include hepati nts have been fatal or life-threatening. DRESS typically, although not exclusively, presents with fever, rash, lymphadenopathy, and/or facial swelling. Other clinical manifestations may include hepatitis, nephritis, hematological abnormalities, myocarditis, or myositis. Sometimes symptoms of DRESS may resemble an acute viral infection. Eosinophilia is often present. Because this disorder is variable in its presentation, other organ systems not noted here may be involved. It is important to note that early manifestations of hypersensitivity, such as fever or lymphadenopathy, may be present even though rash is not evident. If such signs or symptoms are present, discontinue etodolac and evaluate the patient immediately. Fetal Toxicity Premature Closure of Fetal Ductus Arteriosus: Avoid use of NSAIDs, including etodolac, in pregnant women at about 30 weeks gestation and later. NSAIDs including etodolac, increase the risk of premature closure of the fetal ductus arteriosus at approximately this gestational age. Oligohydramnios/Neonatal Renal Impairment: Use of NSAIDs, including etodolac, at about 20 weeks gestation or later in pregnancy may cause fetal renal dysfunction leading to oligo this gestational age. Oligohydramnios/Neonatal Renal Impairment: Use of NSAIDs, including etodolac, at about 20 weeks gestation or later in pregnancy may cause 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. Oligohydramnios is often, but not always, reversible with treatment discontinuation. Complications of prolonged oligohydramnios may, for example, include limb contractures and delayed lung maturation. In some postmarketing cases of impaired neonatal renal function, invasive procedures such as exchange transfusion or dialysis were required. If NSAID treatment is necessary between about 20 weeks and 30 weeks gestation, limit etodolac use to the lowest effective dose and shortest duration possible. Consider ultrasound monitoring of amniotic fluid if etodolac treatment extends beyond 48 hours. Discontinue etodolac if oligohydramnios occurs and follow up according to clinical practice [see PRECAUTIONS; Pregnancy ]. DOSAGE AND ADMINISTRATION Carefully conside reatment extends beyond 48 hours. Discontinue etodolac if oligohydramnios occurs and follow up according to clinical practice [see PRECAUTIONS; Pregnancy ]. DOSAGE AND ADMINISTRATION Carefully consider the potential benefits and risks of etodolac tablets and other treatment options before deciding to use etodolac 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 etodolac tablets, the dose and frequency should be adjusted to suit an individual patient's needs. Dosage adjustment of etodolac tablets is generally not required in patients with mild to moderate renal impairment. Etodolac should be used with caution in such patients, because, as with other NSAIDs, it may further decrease renal function in some patients with impaired renal function (see WARNINGS, Renal Effects ). Analgesia The recommended total daily dose of etodolac for acute pain is up to 1000 mg, given as 200 to 400 mg every 6 to 8 hours. Doses of etodolac greater than 1000 mg/day have not been adequately evaluated in well-controlled trials. Osteoarthritis and Rheumatoid Arthritis The r 00 mg, given as 200 to 400 mg every 6 to 8 hours. Doses of etodolac greater than 1000 mg/day have not been adequately evaluated in well-controlled trials. Osteoarthritis and Rheumatoid Arthritis The recommended starting dose of etodolac for the management of the signs and symptoms of osteoarthritis or rheumatoid arthritis is: 300 mg b.i.d., t.i.d., or 400 mg b.i.d., or 500 mg b.i.d. A lower dose of 600 mg/day may suffice for long-term administration. Physicians should be aware that doses above 1000 mg/day have not been adequately evaluated in well-controlled clinical trials. In chronic conditions, a therapeutic response to therapy with etodolac is sometimes seen within one week of therapy, 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. ADVERSE REACTIONS In patients taking etodolac or other NSAIDs, the most frequently reported adverse experiences occurring in approximately 1 to 10% of patients are: Gastrointestinal experiences including: abdominal pain, constipation, diarrhea, dyspepsia, flatulence, gross bleeding/perforation, heartburn, nausea, GI ulcers (gastric/duodenal), vo of patients are: Gastrointestinal experiences including: abdominal pain, constipation, diarrhea, dyspepsia, flatulence, gross bleeding/perforation, heartburn, nausea, GI ulcers (gastric/duodenal), vomiting. Other events including: abnormal renal function, anemia, dizziness, edema, elevated liver enzymes, headaches, increased bleeding time, pruritis, rashes, tinnitus. Adverse-reaction information for etodolac was derived from 2,629 arthritic patients treated with etodolac in double-blind and open-label clinical trials of 4 to 320 weeks in duration and worldwide postmarketing surveillance studies. In clinical trials, most adverse reactions were mild and transient. The discontinuation rate in controlled clinical trials, because of adverse events, was up to 10% for patients treated with etodolac. New patient complaints (with an incidence greater than or equal to 1%) are listed below by body system. The incidences were determined from clinical trials involving 465 patients with osteoarthritis treated with 300 to 500 mg of etodolac b.i.d. (i.e., 600 to 1000 mg/day). Incidence Greater Than Or Equal To 1% - Probably Causally Related Body as a whole - Chills and fever. Digestive system - D tis treated with 300 to 500 mg of etodolac b.i.d. (i.e., 600 to 1000 mg/day). Incidence Greater Than Or Equal To 1% - Probably Causally Related Body as a whole - Chills and fever. Digestive system - Dyspepsia (10%), abdominal pain 1 , diarrhea 1 , flatulence 1 , nausea 1 , abdominal distension, epigastric pain, abnormal stools, constipation, gastritis, melena, vomiting. Nervous system - Asthenia/malaise 1 , dizziness 1 , depression, nervousness, fatigue. Skin and appendages - Pruritus, rash. Special senses - Blurred vision, tinnitus. Urogenital system - Dysuria, urinary frequency. Musculoskeletal—Arthralgia. 1 Drug-related patient complaints occurring in 3 to 9% of patients treated with etodolac. Drug-related patient complaints occurring in fewer than 3%, but more than 1%, are unmarked. Incidence Less Than 1% - Probably Causally Related (Adverse reactions reported only in worldwide postmarketing experience, not seen in clinical trials, are considered rarer and are italicized.) Body as a whole - Allergic reaction, anaphylactic/anaphylactoid reactions (including shock). Cardiovascular system - Hypertension, congestive heart failure, flushing, palpitations, syncope, vasculitis (includ a whole - Allergic reaction, anaphylactic/anaphylactoid reactions (including shock). Cardiovascular system - Hypertension, congestive heart failure, flushing, palpitations, syncope, vasculitis (including necrotizing and allergic). Digestive system - Thirst, dry mouth, ulcerative stomatitis, anorexia, eructation, elevated liver enzymes, cholestatic hepatitis, hepatitis, cholestatic jaundice, duodenitis, jaundice, hepatic failure, liver necrosis, peptic ulcer with or without bleeding and/or perforation, intestinal ulceration, pancreatitis. Hemic and lymphatic system - Ecchymosis, anemia, thrombocytopenia, bleeding time increased, agranulocytosis, hemolytic anemia, aplastic anemia, leukopenia, neutropenia, pancytopenia. Metabolic and nutritional - Edema, serum creatinine increase, hyperglycemia in previously controlled diabetic patients. Nervous system - Insomnia, somnolence. Respiratory system - Asthma, pulmonary infiltration with eosinophilia . Skin and appendages - Angioedema, sweating, urticaria, exfoliative dermatitis, vesiculobullous rash, cutaneous vasculitis with purpura, Stevens-Johnson Syndrome, toxic epidermal necrolysis, leukocytoclastic vasculitis, hyperpigmentation , ery , urticaria, exfoliative dermatitis, vesiculobullous rash, cutaneous vasculitis with purpura, Stevens-Johnson Syndrome, toxic epidermal necrolysis, leukocytoclastic vasculitis, hyperpigmentation , erythema multiforme. Special senses - Photophobia, transient visual disturbances. Urogenital system - Elevated BUN, renal failure, renal insufficiency, renal papillary necrosis. Incidence Less Than 1% - Causal Relationship Unknown (Medical events occurring under circumstances where causal relationship to etodolac is uncertain. These reactions are listed as alerting information for physicians.) Body as a whole - Infection, headache. Cardiovascular system - Arrhythmias, myocardial infarction, cerebrovascular accident. Digestive system - Esophagitis with or without stricture or cardiospasm, colitis, GI discomfort, burning sensation, blood in stools, gastralgia, upper abdominal discomfort. Metabolic and nutritional - Change in weight. Nervous system - Paresthesia, confusion, irritability. Respiratory system - Bronchitis, bronchospasm, dyspnea, pharyngitis, rhinitis, sinusitis. Skin and appendages - Alopecia, maculopapular rash, photosensitivity, skin peeling. Special senses - Conjunctivitis,