Ropidex

Dexamethasone Sodium Phosphate, Ropivacaine Hydrochloride, Povidine Iodine · Kit · Epidural, Infiltration, Intramuscular

Prescription (Rx)

Uses

By intravenous or intramuscular injection when oral therapy is not feasible: 1. Endocrine Disorders Primary or secondary adrenocortical insufficiency (hydrocortisone or cortisone is the drug of choice; synthetic analogs may be used in conjunction with mineralocorticoids where applicable; in infancy, mineralocorticoid supplementation is of particular importance). Acute adrenocortical insufficiency (hydrocortisone or cortisone is the drug of choice; mineralocorticoid supplementation may be necessary, particularly when synthetic analogs are used). Preoperatively, and in the event of serious trauma or illness, in patients with known adrenal insufficiency or when adrenocortical reserve is doubtful. Shock unresponsive to conventional therapy if adrenocortical insufficiency exists or is suspected. Congenital adrenal hyperplasia Nonsuppurative thyroiditis Hypercalcemia associated with cancer 2. Rheumatic Disorders As adjunctive therapy for short-term administration (to tide the patient over an acute episode or exacerbation) in: Post-traumatic osteoarthritis Synovitis of osteoarthritis Rheumatoid arthritis, including juvenile rheumatoid arthritis (selected cases may require low-dose maintenance therapy). Acute and subacute bursitis Epicondylitis Acute nonspecific tenosynovitis Acute gouty arthritis Psoriatic arthritis Ankylosing spondylitis 3. Collagen Diseases During an exacerbation or as maintenance therapy in selected cases of: Systemic lupus erythematosus Acute rheumatic carditis 4. Dermatologic Diseases Pemphigus Severe erythema multiforme (Stevens-Johnson syndrome) Exfoliative dermatitis Bullous dermatitis herpetiformis Severe seborrheic dermatitis Severe psoriasis Mycosis fungoides 5. Allergic States Control of severe or incapacitating allergic conditions intractable to adequate trials of conventional treatment in: Bronchial asthma Contact dermatitis Atopic dermatitis Serum sickness Seasonal or perennial allergic rhinitis Drug hypersensitivity reactions Urticarial transfusion reactions Acute noninfectious laryngeal edema (epinephrine is the drug of first choice). 6. Ophthalmic Diseases Severe acute and chronic allergic and inflammatory processes involving the eye, such as: Herpes zoster ophthalmicus Iritis, iridocyclitis Chorioretinitis Diffuse posterior uveitis and choroiditis Optic neuritis Sympathetic ophthalmia Anterior segment inflammation Allergic conjunctivitis Keratitis Allergic corneal marginal ulcers 7. Gastrointestinal Diseases To tide the patient over a critical period of the disease in: Ulcerative colitis (systemic therapy) Regional enteritis (systemic therapy) 8. Respiratory Diseases Symptomatic sarcoidosis Berylliosis Fulminating or disseminated pulmonary tuberculosis when used concurrently with appropriate antituberculous chemotherapy. Loeffler’s syndrome not manageable by other means. Aspiration pneumonitis 9. Hematologic Disorders Acquired (autoimmune) hemolytic anemia. Idiopathic thrombocytopenic purpura in adults (IV only; IM administration is contraindicated). Secondary thrombocytopenia in adults Erythroblastopenia (RBC anemia) Congenital (erythroid) hypoplastic anemia 10. Neoplastic Diseases For palliative management of: Leukemias and lymphomas in adults Acute leukemia of childhood 11. Edematous States To induce diuresis or remission of proteinuria in the nephrotic syndrome, without uremia, of the idiopathic type or that due to lupus erythematosus. 12. Miscellaneous Tuberculous meningitis with subarachnoid block or impending block when used concurrently with appropriate antituberculous chemotherapy. Trichinosis with neurologic or myocardial involvement. 13. Diagnostic testing of adrenocortical hyperfunction. 14. Cerebral Edema associated with primary or metastatic brain tumor, craniotomy, or head injury. Use in cerebral edema is not a substitute for careful neurosurgical evaluation and definitive management such as neurosurgery or other specific therapy. INDICATIONS AND USAGE Ropivacaine hydrochloride injection, USP is indicated for the production of local or regional anesthesia for surgery and for acute pain management. Surgical Anesthesia: epidural block for surgery including cesarean section; major nerve block; local infiltration Acute Pain Management: epidural continuous infusion or intermittent bolus, e.g., postoperative or labor; local infiltration For use as an first aid antiseptic pre-operative skin preperation

Dosage and administration

Dexamethasone sodium phosphate injection, 10 mg/mL– For intravenous and intramuscular injection only. Dexamethasone sodium phosphate injection can be given directly from the vial, or it can be added to Sodium Chloride Injection or Dextrose Injection and administered by intravenous drip. Solutions used for intravenous administration or further dilution of this product should be preservative free when used in the neonate, especially the premature infant. When it is mixed with an infusion solution, sterile precautions should be observed. Since infusion solutions generally do not contain preservatives, mixtures should be used within 24 hours. DOSAGE REQUIREMENTS ARE VARIABLE AND MUST BE INDIVIDUALIZED ON THE BASIS OF THE DISEASE AND THE RESPONSE OF THE PATIENT. Intravenous and Intramuscular Injection The initial dosage of dexamethasone sodium phosphate injection varies from 0.5 to 9 mg a day depending on the disease being treated. In less severe diseases doses lower than 0.5 mg may suffice, while in severe diseases doses higher than 9 mg may be required. The initial dosage should be maintained or adjusted until the patient’s response is satisfactory. If a satisfactory clinical response does not occur after a reasonable period of time, discontinue dexamethasone sodium phosphate injection and transfer the patient to other therapy. After a favorable initial response, the proper maintenance dosage should be determined by decreasing the initial dosage in small amounts to the lowest dosage that maintains an adequate clinical response. Patients should be observed closely for signs that might require dosage adjustment, including changes in clinical status resulting from remissions or exacerbations of the disease, individual drug responsiveness, and the effect of stress (e.g., surgery, infection, trauma). During stress it may be necessary to increase dosage temporarily. If the drug is to be stopped after more than a few days of treatment, it usually should be withdrawn gradually. When the intravenous route of administration is used, dosage usually should be the same as the oral dosage. In certain overwhelming, acute, life-threatening situations, however, administration in dosages exceeding the usual dosages may be justified and may be in multiples of the oral dosages. The slower rate of absorption by intramuscular administration should be recognized. Shock There is a tendency in current medical practice to use high (pharmacologic) doses of corticosteroids for the treatment of unresponsive shock. The following dosages of dexamethasone sodium phosphate injection have been suggested by various authors: Author Dosage Cavanagh 1 3 mg/kg of body weight per 24 hours by constant intravenous infusion after an initial intravenous injection of 20 mg Dietzman 2 2 to 6 mg/kg of body weight as a single intravenous injection Frank 3 40 mg initially followed by repeat intravenous injection every 4 to 6 hours while shock persists Oaks 4 40 mg initially followed by repeat intravenous injection every 2 to 6 hours while shock persists Schumer 5 1 mg/kg of body weight as a single intravenous injection Administration of high dose corticosteroid therapy should be continued only until the patient’s condition has stabilized and usually not longer than 48 to 72 hours. Although adverse reactions associated with high dose, short-term corticosteroid therapy are uncommon, peptic ulceration may occur. Cerebral Edema Dexamethasone sodium phosphate injection is generally administered initially in a dosage of 10 mg intravenously followed by four mg every six hours intramuscularly until the symptoms of cerebral edema subside. Response is usually noted within 12 to 24 hours and dosage may be reduced after two to four days and gradually discontinued over a period of five to seven days. For palliative management of patients with recurrent or inoperable brain tumors, maintenance therapy with 2 mg two or three times a day may be effective. Acute Allergic Disorders In acute, self-limited allergic disorders or acute exacerbations of chronic allergic disorders, the following dosage schedule combining parenteral and oral therapy is suggested: Dexamethasone sodium phosphate injection, first day , 4 or 8 mg intramuscularly. Dexamethasone tablets, 0.75 mg: second and third days, 4 tablets in two divided doses each day; fourth day , 2 tablets in two divided doses; fifth and sixth days, 1 tablet each day; seventh day, no treatment; eighth day, follow-up visit. This schedule is designed to ensure adequate therapy during acute episodes, while minimizing the risk of overdosage in chronic cases. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever the solution and container permit. Intravenous and Intramuscular Injection The initial dosage of dexamethasone sodium phosphate injection varies from 0.5 to 9 mg a day depending on the disease being treated. In less severe diseases doses lower than 0.5 mg may suffice, while in severe diseases doses higher than 9 mg may be required. The initial dosage should be maintained or adjusted until the patient’s response is satisfactory. If a satisfactory clinical response does not occur after a reasonable period of time, discontinue dexamethasone sodium phosphate injection and transfer the patient to other therapy. After a favorable initial response, the proper maintenance dosage should be determined by decreasing the initial dosage in small amounts to the lowest dosage that maintains an adequate clinical response. Patients should be observed closely for signs that might require dosage adjustment, including changes in clinical status resulting from remissions or exacerbations of the disease, individual drug responsiveness, and the effect of stress (e.g., surgery, infection, trauma). During stress it may be necessary to increase dosage temporarily.

Contraindications

Systemic fungal infections (see WARNINGS regarding amphotericin B). Hypersensitivity to any component of this product (see WARNINGS ) . CONTRAINDICATIONS Ropivacaine hydrochloride injection is contraindicated in patients with a known hypersensitivity to ropivacaine or to any local anesthetic agent of the amide type.

Warnings

Because rare instances of anaphylactoid reactions have occurred in patients receiving parenteral corticosteroid therapy, appropriate precautionary measures should be taken prior to administration, especially when the patient has a history of allergy to any drug. Anaphylactoid and hypersensitivity reactions have been reported for dexamethasone sodium phosphate injection (see ADVERSE REACTIONS ). Corticosteroids may exacerbate systemic fungal infections and, therefore, should not be used in the presence of such infections unless they are needed to control drug reactions due to amphotericin B. Moreover, there have been cases reported in which concomitant use of amphotericin B and hydrocortisone was followed by cardiac enlargement and congestive failure. In patients on corticosteroid therapy subjected to any unusual stress, increased dosage of rapidly acting corticosteroids before, during, and after the stressful situation is indicated. Drug-induced secondary adrenocortical insufficiency may result from too rapid withdrawal of corticosteroids and may be minimized by gradual reduction of dosage. This type of relative insufficiency may persist for months after discontinuation of therapy; therefore, in any situation of stress occurring during that period, hormone therapy should be reinstituted. If the patient is receiving steroids already, dosage may have to be increased. Since mineralocorticoid secretion may be impaired, salt and/or a mineralocorticoid should be administered concurrently. Corticosteroids may mask some signs of infection, and new infections may appear during their use. There may be decreased resistance and inability to localize infection when corticosteroids are used. Moreover, corticosteroids may affect the nitroblue-tetrazolium test for bacterial infection and produce false negative results. In cerebral malaria, a double-blind trial has shown that the use of corticosteroids is associated with prolongation of coma and a higher incidence of pneumonia and gastrointestinal bleeding. Corticosteroids may activate latent amebiasis. Therefore, it is recommended that latent or active amebiasis be ruled out before initiating corticosteroid therapy in any patient who has spent time in the tropics or in any patient with unexplained diarrhea. Prolonged use of corticosteroids may produce posterior subcapsular cataracts, glaucoma with possible damage to the optic nerves, and may enhance the establishment of secondary ocular infections due to fungi or viruses. Average and large doses of cortisone or hydrocortisone can cause elevation of blood pressure, salt and water retention, and increased excretion of potassium. These effects are less likely to occur with the synthetic derivatives except when used in large doses. Dietary salt restriction and potassium supplementation may be necessary. All corticosteroids increase calcium excretion. Administration of live virus vaccines, including smallpox, is contraindicated in individuals receiving immunosuppressive doses of corticosteroids. If inactivated viral or bacterial vaccines are administered to individuals receiving immunosuppressive doses of corticosteroids, the expected serum antibody response may not be obtained. However, immunization procedures may be undertaken in patients who are receiving corticosteroids as replacement therapy, e.g., for Addison’s disease. Patients who are on drugs which suppress the immune system are more susceptible to infections than healthy individuals. Chickenpox and measles, for example, can have a more serious or even fatal course in non-immune children or adults on corticosteroids. In such children or adults who have not had these diseases, particular care should be taken to avoid exposure. The risk of developing a disseminated infection varies among individuals and can be related to the dose, route and duration of corticosteroid administration as well as to the underlying disease. If exposed to chickenpox, prophylaxis with varicella zoster immune globulin (VZIG) may be indicated. If chickenpox develops, treatment with antiviral agents may be considered. If exposed to measles, prophylaxis with immune globulin (IG) may be indicated. (See the respective package inserts for VZIG and IG for complete prescribing information). The use of dexamethasone sodium phosphate injection in active tuberculosis should be restricted to those cases of fulminating or disseminated tuberculosis in which the corticosteroid is used for the management of the disease in conjunction with an appropriate antituberculous regimen. If corticosteroids are indicated in patients with latent tuberculosis or tuberculin reactivity, close observation is necessary as reactivation of the disease may occur. During prolonged corticosteroid therapy, these patients should receive chemoprophylaxis. Literature reports suggest an apparent association between use of corticosteroids and left ventricular free wall rupture after a recent myocardial infarction; therefore, therapy with corticosteroids should be used with great caution in these patients. Serious Neurologic Adverse Reactions with Epidural Administration Serious neurologic events, some resulting in death, have been reported with epidural injection of corticosteroids. Specific events reported include, but are not limited to, spinal cord infarction, paraplegia, quadriplegia, cortical blindness, and stroke. These serious neurologic events have been reported with and without use of fluoroscopy. The safety and effectiveness of epidural administration of corticosteroids has not been established, and corticosteroids are not approved for this use. Usage in Pregnancy Since adequate human reproduction studies have not been done with corticosteroids, use of these drugs in pregnancy or in women of childbearing potential requires that the anticipated benefits be weighed against the possible hazards to the mother and embryo or fetus.

Precautions

This product, like many other steroid formulations, is sensitive to heat. Therefore, it should not be autoclaved when it is desirable to sterilize the exterior of the vial. Following prolonged therapy, withdrawal of corticosteroids may result in symptoms of the corticosteroid withdrawal syndrome including fever, myalgia, arthralgia, and malaise. This may occur in patients even without evidence of adrenal insufficiency. There is an enhanced effect of corticosteroids in patients with hypothyroidism and in those with cirrhosis. Corticosteroids should be used cautiously in patients with ocular herpes simplex for fear of corneal perforation. The lowest possible dose of corticosteroid should be used to control the condition under treatment, and when reduction in dosage is possible, the reduction must be gradual. Psychic derangements may appear when corticosteroids are used, ranging from euphoria, insomnia, mood swings, personality changes, and severe depression to frank psychotic manifestations. Also, existing emotional instability or psychotic tendencies may be aggravated by corticosteroids. Aspirin should be used within caution in conjunction with corticosteroids in hypoprothrombinemia. Steroids should be used with caution in nonspecific ulcerative colitis, if there is a probability of impending perforation, abscess, or other pyogenic infection, also in diverticulitis, fresh intestinal anastomoses, active or latent peptic ulcer, renal insufficiency, hypertension, osteoporosis, and myasthenia gravis. Signs of peritoneal irritation following gastrointestinal perforation in patients receiving large doses of corticosteroids may be minimal or absent. Fat embolism has been reported as a possible complication of hypercortisonism. When large doses are given, some authorities advise that antacids be administered between meals to help prevent peptic ulcer. Steroids may increase or decrease motility and number of spermatozoa in some patients. Phenytoin, phenobarbital, ephedrine, and rifampin may enhance the metabolic clearance of corticosteroids resulting in decreased blood levels and lessened physiologic activity, thus requiring adjustment in corticosteroid dosage. These interactions may interfere with dexamethasone suppression tests which should be interpreted with caution during administration of these drugs. False negative results in the dexamethasone suppression test (DST) in patients being treated with indomethacin have been reported. Thus, results of the DST should be interpreted with caution in these patients. The prothrombin time should be checked frequently in patients who are receiving corticosteroids and coumarin anticoagulants at the same time because of reports that corticosteroids have altered the response to these anticoagulants. Studies have shown that the usual effect produced by adding corticosteroids is inhibition of response to coumarins, although there have been some conflicting reports of potentiation not substantiated by studies. When corticosteroids are administered concomitantly with potassium-depleting diuretics, patients should be observed closely for development of hypokalemia. The slower rate of absorption by intramuscular administration should be recognized. Information for Patients Susceptible patients who are on immunosuppressant doses of corticosteroids should be warned to avoid exposure to chickenpox or measles. Patients should also be advised that if they are exposed, medical advice should be sought without delay. Pediatric Use Growth and development of infants and children patients on prolonged corticosteroid therapy should be carefully followed. Information for Patients Susceptible patients who are on immunosuppressant doses of corticosteroids should be warned to avoid exposure to chickenpox or measles. Patients should also be advised that if they are exposed, medical advice should be sought without delay. Pediatric Use Growth and development of infants and children patients on prolonged corticosteroid therapy should be carefully followed. PRECAUTIONS General The safe and effective use of local anesthetics depends on proper dosage, correct technique, adequate precautions and readiness for emergencies. Resuscitative equipment, oxygen and other resuscitative drugs should be available for immediate use (see WARNINGS and ADVERSE REACTIONS ). The lowest dosage that results in effective anesthesia should be used to avoid high plasma levels and serious adverse events. Injections should be made slowly and incrementally, with frequent aspirations before and during the injection to avoid intravascular injection. When a continuous catheter technique is used, syringe aspirations should also be performed before and during each supplemental injection. During the administration of epidural anesthesia, it is recommended that a test dose of a local anesthetic with a fast onset be administered initially and that the patient be monitored for central nervous system and cardiovascular toxicity, as well as for signs of unintended intrathecal administration before proceeding. When clinical conditions permit, consideration should be given to employing local anesthetic solutions, which contain epinephrine for the test dose because circulatory changes compatible with epinephrine may also serve as a warning sign of unintended intravascular injection. An intravascular injection is still possible even if aspirations for blood are negative. Administration of higher than recommended doses of ropivacaine hydrochloride to achieve greater motor blockade or increased duration of sensory blockade may result in cardiovascular depression, particularly in the event of inadvertent intravascular injection. Tolerance to elevated blood levels varies with the physical condition of the patient. Debilitated, elderly patients and acutely ill patients should be given reduced doses commensurate with their age and physical condition.

Side effects

Fluid and electrolyte disturbances: Sodium retention Fluid retention Congestive heart failure in susceptible patients Potassium loss Hypokalemic alkalosis Hypertension Musculoskeletal: Muscle weakness Steroid myopathy Loss of muscle mass Osteoporosis Vertebral compression fractures Aseptic necrosis of femoral and humeral heads Tendon rupture Pathologic fracture of long bones Gastrointestinal: Peptic ulcer with possible subsequent perforation and hemorrhage Perforation of the small and large bowel; particularly in patients with inflammatory bowel disease Pancreatitis Abdominal distention Ulcerative esophagitis Dermatologic: Impaired wound healing Thin fragile skin Petechiae and ecchymoses Erythema Increased sweating May suppress reactions to skin tests Burning or tingling, especially in the perineal area (after IV injection) Other cutaneous reactions, such as allergic dermatitis, urticaria, angioneurotic edema Neurologic: Convulsions Increased intracranial pressure with papilledema (pseudotumor cerebri) usually after treatment Vertigo Headache Psychic disturbances Endocrine: Menstrual irregularities Development of cushingoid state Suppression of growth in pediatric patients Secondary adrenocortical and pituitary unresponsiveness, particularly in times of stress, as in trauma, surgery, or illness Decreased carbohydrate tolerance Manifestations of latent diabetes mellitus Increased requirements for insulin or oral hypoglycemic agents in diabetics Hirsutism Ophthalmic: Posterior subcapsular cataracts Increased intraocular pressure Glaucoma Exophthalmos Retinopathy of prematurity Metabolic: Negative nitrogen balance due to protein catabolism Cardiovascular: Myocardial rupture following recent myocardial infarction (see WARNINGS ) Hypertrophic cardiomyopathy in low birth weight infants Other: Anaphylactoid or hypersensitivity reactions Thromboembolism Weight gain Increased appetite Nausea Malaise Hiccups The following additional adverse reactions are related to parenteral corticosteroid therapy: Hyperpigmentation or hypopigmentation Subcutaneous and cutaneous atrophy Sterile abscess Charcot-like arthropathy ADVERSE REACTIONS Reactions to ropivacaine are characteristic of those associated with other amide-type local anesthetics. A major cause of adverse reactions to this group of drugs may be associated with excessive plasma levels, which may be due to overdosage, unintentional intravascular injection or slow metabolic degradation. The reported adverse events are derived from clinical studies conducted in the U.S. and other countries. The reference drug was usually bupivacaine. The studies used a variety of premedications, sedatives, and surgical procedures of varying length. A total of 3,988 patients have been exposed to ropivacaine hydrochloride at concentrations up to 1% in clinical trials. Each patient was counted once for each type of adverse event. Incidence ≥ 5% For the indications of epidural administration in surgery, cesarean section, postoperative pain management, peripheral nerve block, and local infiltration, the following treatment-emergent adverse events were reported with an incidence of ≥5% in all clinical studies (N=3988): hypotension (37%), nausea (24.8%), vomiting (11.6%), bradycardia (9.3%), fever (9.2%), pain (8%), postoperative complications (7.1%), anemia (6.1%), paresthesia (5.6%), headache (5.1%), pruritus (5.1%), and back pain (5%). Incidence 1 to 5% Urinary retention, dizziness, rigors, hypertension, tachycardia, anxiety, oliguria, hypoesthesia, chest pain, hypokalemia, dyspnea, cramps, and urinary tract infection. Incidence in Controlled Clinical Trials The reported adverse events are derived from controlled clinical studies with ropivacaine hydrochloride (concentrations ranged from 0.125% to 1% for ropivacaine hydrochloride and 0.25% to 0.75% for bupivacaine) in the U.S. and other countries involving 3,094 patients. Table 3A and 3B list adverse events (number and percentage) that occurred in at least 1% of ropivacaine hydrochloride-treated patients in these studies. The majority of patients receiving concentrations higher than 5 mg/mL (0.5%) were treated with ropivacaine hydrochloride.

Drug interactions

Drug Interactions Specific trials studying the interaction between ropivacaine and class III antiarrhythmic drugs (e.g., amiodarone) have not been performed, but caution is advised (see WARNINGS ). Ropivacaine hydrochloride should be used with caution in patients receiving other local anesthetics or agents structurally related to amide-type local anesthetics, since the toxic effects of these drugs are additive. Cytochrome P4501A2 is involved in the formation of 3-hydroxy ropivacaine, the major metabolite. In vivo, the plasma clearance of ropivacaine was reduced by 70% during coadministration of fluvoxamine (25 mg bid for 2 days), a selective and potent CYP1A2 inhibitor. Thus strong inhibitors of cytochrome P4501A2, such as fluvoxamine, given concomitantly during administration of ropivacaine hydrochloride, can interact with ropivacaine hydrochloride leading to increased ropivacaine plasma levels. Caution should be exercised when CYP1A2 inhibitors are coadministered. Possible interactions with drugs known to be metabolized by CYP1A2 via competitive inhibition such as theophylline and imipramine may also occur. Coadministration of a selective and potent inhibitor of CYP3A4, ketoconazole (100 mg bid for 2 days with ropivacaine infusion administered 1 hour after ketoconazole) caused a 15% reduction in in vivo plasma clearance of ropivacaine. Patients who are administered local anesthetics are at increased risk of developing methemoglobinemia when concurrently exposed to the following drugs, which could include other local anesthetics: Examples of Drugs Associated with Methemoglobinemia: Class Examples Nitrates/Nitrites nitric oxide, nitroglycerin, nitroprusside, nitrous oxide Local anesthetics articaine, benzocaine, bupivacaine, lidocaine, mepivacaine, prilocaine, procaine, ropivacaine, tetracaine Antineoplastic agents cyclophosphamide, flutamide, hydroxyurea, ifosfamide, rasburicase Antibiotics dapsone, nitrofurantoin, para-aminosalicylic acid, sulfonamides Antimalarials chloroquine, primaquine Anticonvulsants Phenobarbital, phenytoin, sodium valproate Other drugs acetaminophen, metoclopramide, quinine, sulfasalazine

Pregnancy

Pregnancy Category B Reproduction toxicity studies have been performed in pregnant New Zealand white rabbits and Sprague-Dawley rats. During gestation days 6 to 18, rabbits received 1.3, 4.2, or 13 mg/kg/day subcutaneously. In rats, subcutaneous doses of 5.3, 11 and 26 mg/kg/day were administered during gestation days 6 to 15. No teratogenic effects were observed in rats and rabbits at the highest doses tested. The highest doses of 13 mg/kg/day (rabbits) and 26 mg/kg/day (rats) are approximately 1/3 of the maximum recommended human dose (epidural, 770 mg/24 hours) based on a mg/m 2 basis. In 2 prenatal and postnatal studies, the female rats were dosed daily from day 15 of gestation to day 20 postpartum. The doses were 5.3, 11 and 26 mg/kg/day subcutaneously. There were no treatment-related effects on late fetal development, parturition, lactation, neonatal viability, or growth of the offspring. In another study with rats, the males were dosed daily for 9 weeks before mating and during mating. The females were dosed daily for 2 weeks before mating and then during the mating, pregnancy, and lactation, up to day 42 post coitus. At 23 mg/kg/day, an increased loss of pups was observed during the first 3 days postpartum. The effect was considered secondary to impaired maternal care due to maternal toxicity. There are no adequate or well-controlled studies in pregnant women of the effects of ropivacaine hydrochloride on the developing fetus. Ropivacaine hydrochloride should only be used during pregnancy if the benefits outweigh the risk. Teratogenicity studies in rats and rabbits did not show evidence of any adverse effects on organogenesis or early fetal development in rats (26 mg/kg sc) or rabbits (13 mg/kg). The doses used were approximately equal to total daily dose based on body surface area. There were no treatment-related effects on late fetal development, parturition, lactation, neonatal viability, or growth of the offspring in 2 perinatal and postnatal studies in rats, at dose levels equivalent to the maximum recommended human dose based on body surface area. In another study at 23 mg/kg, an increased pup loss was seen during the first 3 days postpartum, which was considered secondary to impaired maternal care due to maternal toxicity.

Pediatric use

Pediatric Use The safety and efficacy of ropivacaine hydrochloride in pediatric patients have not been established.

Geriatric use

Geriatric Use Of the 2,978 subjects that were administered ropivacaine hydrochloride injection in 71 controlled and uncontrolled clinical studies, 803 patients (27%) were 65 years of age or older which includes 127 patients (4%) 75 years of age and over. Ropivacaine hydrochloride injection was found to be safe and effective in the patients in these studies. Clinical data in one published article indicate that differences in various pharmacodynamic measures were observed with increasing age. In one study, the upper level of analgesia increased with age, the maximum decrease of mean arterial pressure (MAP) declined with age during the first hour after epidural administration, and the intensity of motor blockade increased with age. This drug and its metabolites are known to be excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Elderly patients are more likely to have decreased hepatic, renal, or cardiac function, as well as concomitant disease. Therefore, care should be taken in dose selection, starting at the low end of the dosage range, and it may be useful to monitor renal function (see PHARMACOKINETICS, Elimination ).

Overdosage

Reports of acute toxicity and/or death following overdosage of glucocorticoids are rare. In the event of overdosage, no specific antidote is available; treatment is supportive and symptomatic. The oral LD 50 of dexamethasone in female mice was 6.5 g/kg. The intravenous LD 50 of dexamethasone sodium phosphate in female mice was 794 mg/kg. OVERDOSAGE Acute emergencies from local anesthetics are generally related to high plasma levels encountered, or large doses administered, during therapeutic use of local anesthetics or to unintended subarachnoid or intravascular injection of local anesthetic solution (see ADVERSE REACTIONS , WARNINGS , and PRECAUTIONS ). MANAGEMENT OF LOCAL ANESTHETIC EMERGENCIES Therapy with ropivacaine hydrochloride should be discontinued at the first sign of toxicity. No specific information is available for the treatment of toxicity with ropivacaine hydrochloride; therefore, treatment should be symptomatic and supportive. The first consideration is prevention, best accomplished by incremental injection of ropivacaine hydrochloride, careful and constant monitoring of cardiovascular and respiratory vital signs and the patient’s state of consciousness after each local anesthetic and during continuous infusion. At the first sign of change in mental status, oxygen should be administered. The first step in the management of systemic toxic reactions, as well as underventilation or apnea due to unintentional subarachnoid injection of drug solution, consists of immediate attention to the establishment and maintenance of a patent airway and effective assisted or controlled ventilation with 100% oxygen with a delivery system capable of permitting immediate positive airway pressure by mask. Circulation should be assisted as necessary. This may prevent convulsions if they have not already occurred. If necessary, use drugs to control convulsions. Intravenous barbiturates, anticonvulsant agents, or muscle relaxants should only be administered by those familiar with their use. Immediately after the institution of these ventilatory measures, the adequacy of the circulation should be evaluated. Supportive treatment of circulatory depression may require administration of intravenous fluids, and, when appropriate, a vasopressor dictated by the clinical situation (such as ephedrine or epinephrine to enhance myocardial contractile force). Should cardiac arrest occur, prolonged resuscitative efforts may be required to improve the probability of a successful outcome. The mean dosages of ropivacaine producing seizures, after intravenous infusion in dogs, nonpregnant and pregnant sheep were 4.9, 6.1 and 5.9 mg/kg, respectively. These doses were associated with peak arterial total plasma concentrations of 11.4, 4.3 and 5 mcg/mL, respectively. In human volunteers given intravenous ropivacaine hydrochloride, the mean (min-max) maximum tolerated total and free arterial plasma concentrations were 4.3 (3.4 to 5.3) and 0.6 (0.3 to 0.9) mcg/mL respectively, at which time moderate CNS symptoms (muscle twitching) were noted. Clinical data from patients experiencing local anesthetic induced convulsions demonstrated rapid development of hypoxia, hypercarbia and acidosis within a minute of the onset of convulsions. These observations suggest that oxygen consumption and carbon dioxide production are greatly increased during local anesthetic convulsions and emphasize the importance of immediate and effective ventilation with oxygen which may avoid cardiac arrest. If difficulty is encountered in the maintenance of a patent airway or if prolonged ventilatory support (assisted or controlled) is indicated, endotracheal intubation, employing drugs and techniques familiar to the clinician, may be indicated after initial administration of oxygen by mask. The supine position is dangerous in pregnant women at term because of aortocaval compression by the gravid uterus. Therefore, during treatment of systemic toxicity, maternal hypotension or fetal bradycardia following regional block, the parturient should be maintained in the left lateral decubitus position if possible, or manual displacement of the uterus off the great vessels should be accomplished. Resuscitation of obstetrical patients may take longer than resuscitation of non-pregnant patients and closed-chest cardiac compression may be ineffective. Rapid delivery of the fetus may improve the response to resuscitative efforts.

Description

Dexamethasone Sodium Phosphate Injection, USP, is a water-soluble inorganic ester of dexamethasone which produces a rapid response even when injected intramuscularly. Dexamethasone Sodium Phosphate, USP chemically is Pregna-1,4-diene-3,20-dione, 9-fluoro- 11,17-dihydroxy-16-methyl-21-(phosphonooxy)-, disodium salt, (11ß, 16α). It occurs as a white to creamy white powder, is exceedingly hygroscopic, is soluble in water and its solutions have a pH between 7.0 and 8.5. It has the following structural formula: Each mL of Dexamethasone Sodium Phosphate Injection, USP (Preservative Free) contains dexamethasone sodium phosphate, USP equivalent to 10 mg dexamethasone phosphate; 24.75 mg sodium citrate, dihydrate; and Water for Injection, q.s. pH adjusted with citric acid or sodium hydroxide, if necessary. pH: 7.0 to 8.5. structure DESCRIPTION Ropivacaine hydrochloride injection, USP contains ropivacaine hydrochloride which is a member of the amino amide class of local anesthetics. Ropivacaine hydrochloride injection, USP is a clear, colorless, sterile, isotonic solution free from visible particles that contains the enantiomerically pure drug substance, sodium chloride for isotonicity and water for injection. Sodium hydroxide and/or hydrochloric acid may be used for pH adjustment. It is administered parenterally. Ropivacaine hydrochloride USP is chemically described as S-(-)-1-propyl-2’,6’-pipecoloxylidide hydrochloride monohydrate. The drug substance is a white crystalline powder, with the following structural formula: At 25°C ropivacaine hydrochloride has a solubility of 53.8 mg/mL in water, a distribution ratio between n-octanol and phosphate buffer at pH 7.4 of 14:1 and a pKa of 8.07 in 0.1 M KCl solution. The pKa of ropivacaine is approximately the same as bupivacaine (8.1) and is similar to that of mepivacaine (7.7). However, ropivacaine has an intermediate degree of lipid solubility compared to bupivacaine and mepivacaine. Ropivacaine hydrochloride injection, USP is preservative-free and is available in single dose containers in 5 mg/mL (0.5%) concentrations. The specific gravity of ropivacaine hydrochloride injection, USP solutions range from 1.002 to 1.005 at 25°C. Ropivacaine Hydrochloride Chemical Structure

How supplied

Dexamethasone Sodium Phosphate Injection, USP (Preservative Free) equivalent to 10 mg dexamethasone phosphate, is supplied in a single dose vial as follows: Product No. NDC No. Strength Vial Size 500601 63323-506-01 10 mg per mL 1 mL vial, packaged in twenty-fives. This container closure is not made with natural rubber latex. Storage Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature]. Sensitive to heat. Do not autoclave. Protect from freezing. Protect from light. Single dose vials–Store in container until time of use. Discard unused portion. Storage Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature]. Sensitive to heat. Do not autoclave. Protect from freezing. Protect from light. Single dose vials–Store in container until time of use. Discard unused portion. HOW SUPPLIED Ropivacaine hydrochloride injection, USP is a clear, colorless, sterile, isotonic solution free from visible particles and is supplied as follows: Ropivacaine hydrochloride injection USP, 0.5 % 100 mg/20 mL (5 mg/mL): 20 mL Single Dose Vials in a Carton of 25 NDC 55150-197-20 The solubility of ropivacaine is limited at pH above 6. Thus, care must be taken as precipitation may occur if ropivacaine hydrochloride injection, USP is mixed with alkaline solutions. Disinfecting agents containing heavy metals, which cause release of respective ions (mercury, zinc, copper, etc.) should not be used for skin or mucous membrane disinfection since they have been related to incidents of swelling and edema. When chemical disinfection of the container surface is desired, either isopropyl alcohol (91%) or ethyl alcohol (70%) is recommended. It is recommended that chemical disinfection be accomplished by wiping the vial stopper thoroughly with cotton or gauze that has been moistened with the recommended alcohol just prior to use. Glass containers may, as an alternative, be autoclaved once. Stability has been demonstrated using a targeted F 0 of 7 minutes at 121°C. Solutions should be stored at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature]. The vial stoppers are not made with natural rubber latex. These products are intended for single dose and are free from preservatives. Any solution remaining from an opened container should be discarded promptly. In addition, continuous infusion bottles should not be left in place for more than 24 hours. Distributed by: AuroMedics Pharma LLC 279 Princeton-Hightstown Rd. E. Windsor, NJ 08520 Manufactured by: Aurobindo Pharma Limited Hyderabad - 500038 India Revised: March 2019

Patient information

Information for Patients When appropriate, patients should be informed in advance that they may experience temporary loss of sensation and motor activity in the anesthetized part of the body following proper administration of lumbar epidural anesthesia. Also, when appropriate, the physician should discuss other information including adverse reactions in the ropivacaine hydrochloride package insert. Inform patients that use of local anesthetics may cause methemoglobinemia, a serious condition that must be treated promptly. Advise patients or caregivers to seek immediate medical attention if they or someone in their care experience the following signs or symptoms: pale, gray, or blue colored skin (cyanosis); headache; rapid heart rate; shortness of breath; lightheadedness; or fatigue.

Label text from the FDA structured product label by Asclemed USA, Inc. (revised Oct 4, 2024). Long sections are shortened; the complete label is on DailyMed.

Ropidex NDC products (1)

NDC	Strength & form	Labeler	Type
76420-219	Kit	Asclemed USA, Inc.	UNAPPROVED DRUG OTHER

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Ropidex is listed by 1 labeler in the FDA NDC directory, including Asclemed USA, Inc..