Ophth-neodex

Uses

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, pre operatively 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

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 sub-acute bursitis, epicondylitis, acute nonspecific tenosynovitis, acute gouty arthritis, psoriatic arthritis, ankylosing spondylitis.

Collagen diseases: During an exacerbation or as maintenance therapy in selected cases of Systemic lupus erythematosus and acute rheumatic carditis

Dermatologic diseases: Pemphigus,Severe erythema multiforme (Stevens-Johnson syndrome), Exfoliative dermatitis, Bullous dermatitis herpetiformis, Severe seborrheic dermatitis,Severe psoriasis, Mycosis fungoides

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 non-infectious laryngeal edema (epinephrine is the drug of first choice)

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.

Gastrointestinal diseases: To tide the patient over a critical period of the disease in ulcerative colitis (systemic therapy), regional enteritis (systemic therapy) Respiratory diseases Symptomatic sarcoidosis, berylliosis, fulminating or disseminated pulmonary tuberculosis when used concurrently with appropriate anti-tuberculous chemotherapy, Loeffler's syndrome not manageable by other means, aspiration pneumonitis.

Hematologic disorders: Acquired (autoimmune) hemolytic anemia, idiopathic thrombocytopenic purpura in adults (I.V. only: I.M administration is contraused), secondary thrombocytopenia in adults, erythroblastopenia (RBC anemia), congenital (erythroid) hypoplasticanemia

Neoplastic diseases: For palliative management of leukemias and lymphomas in adults, acute leukemia of childhood.

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.

Miscellaneous: Tuberculous meningitis with subarachnoid block or impending block when used concurrently with appropriate antituberculous chemotherapy,Trichinosis with neurologic or myocardial involvement

Cerebral Edema: 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.May also be useful in cystic tumors of an aponeurosis or tendon (ganglia).

Neomycin is an aminoglycoside antibiotic agent used orally and topically to treat a wide variety of infections in the body.

Oral neomycin sulfate is indicated as an adjunctive therapy in hepatic coma (portal-system encephalopathy) by reducing ammonia-forming bacteria in the intestinal tract. It is strongly recommended that oral neomycin is only used in infections that are proven or strongly suspected to be caused by susceptible bacteria to reduce the risk of the development of drug-resistant bacteria.

Neomycin, in combination with polymyxin B sulfates and hydrocortisone in otic suspensions, is used in the treatment of superficial bacterial infections of the external auditory canal caused by organisms susceptible to the antibiotics. This otic formulation is also used in the treatment of infections of mastoidectomy and fenestration cavities caused by organisms susceptible to the antibiotics.

The ophthalmic solution containing neomycin in combination with polymyxin B sulfates and dexamethasone is used to treat steroid-responsive inflammatory ocular conditions for which a corticosteroid is indicated and where bacterial infection or a risk of bacterial infection exists.

Acute infections caused by susceptible strains of Pseudomonas aeruginosa:

Polymyxin B Sulfate is a drug of choice in the treatment of infections of the urinary tract, meninges, and bloodstream caused by susceptible strains of Pseudomonas aeruginosa.

It may be used for serious infections caused by susceptible strains of the following organisms, when less potentially toxic drugs are ineffective or contraused:

• H. influenzae: Specifically meningeal infections
• Escherichia coli: Specifically urinary tract infections
• Aerobacter aerogenes: Specifically bacteremia
• Klebsiella pneumoniae: Specifically bacteremia

Ophth-neodex is also used to associated treatment for these conditions: Acne Rosacea, Acute Gouty Arthritis, Acute Otitis Externa, Acute Otitis Media, Adrenal cortical hypofunctions, Adrenocortical Hyperfunction, Alopecia Areata (AA), Ankylosing Spondylitis (AS), Anterior Segment Inflammation, Aspiration Pneumonitis, Asthma, Atopic Dermatitis (AD), Berylliosis, Bullous dermatitis herpetiformis, Bursitis, Chorioretinitis, Choroiditis, Congenital Adrenal Hyperplasia (CAH), Congenital Hypoplastic Anemia, Conjunctivitis, Conjunctivitis allergic, Corneal Inflammation, Cushing's Syndrome, Dermatitis, Dermatitis exfoliative generalised, Dermatitis, Contact, Diabetic Macular Edema (DME), Discoid Lupus Erythematosus (DLE), Drug hypersensitivity reaction, Edema of the cerebrum, Epicondylitis, Episcleritis, Erythroblastopenia, Eye Infections, Eye allergy, Eye swelling, Glaucoma, Hypercalcemia, Idiopathic Thrombocytopenic Purpura, Infection, Inflammation, Inflammation of the External Auditory Canal, Intraocular Inflammation, Iridocyclitis, Iritis, Keloid Scars, Leukemia, Acute, Lichen Planus (LP), Lichen simplex chronicus, Loeffler's syndrome, Macular Edema, Malignant Lymphomas, Middle ear inflammation, Mucosal Inflammation of the eye, Multiple Myeloma (MM), Muscle Inflammation caused by Cataract Surgery of the eye, Mycosis Fungoides (MF), Necrobiosis lipoidica diabeticorum, Noninfectious Posterior Uveitis, Ocular Infections, Irritations and Inflammations, Ocular Inflammation, Ocular Inflammation and Pain, Ocular Irritation, Ophthalmia, Sympathetic, Optic Neuritis, Otitis Externa, Pemphigus, Perennial Allergic Rhinitis (PAR), Phlyctenular keratoconjunctivitis, Post-traumatic Osteoarthritis, Postoperative Infections of the eyes caused by susceptible bacteria, Regional Enteritis, Rheumatoid Arthritis, Rheumatoid Arthritis, Juvenile, Sarcoidosis, Scleritis, Seasonal Allergic Conjunctivitis, Seasonal Allergic Rhinitis, Secondary thrombocytopenia, Serum Sickness, Severe Seborrheic Dermatitis, Stevens-Johnson Syndrome, Synovitis, Systemic Lupus Erythematosus (SLE), Trichinosis, Tuberculosis (TB), Tuberculosis Meningitis, Ulcerative Colitis, Uveitis, Vernal Keratoconjunctivitis, Acquired immune hemolytic anemia, Acute nonspecific tenosynovitis, Acute rheumatic carditis, Corticosteroid-responsive dermatoses, Ear infection-not otherwise specified caused by susceptible bacteria, Granuloma annulare lesions, Non-suppurative Thyroiditis, Ocular bacterial infections, Severe Psoriasis, Steroid-responsive inflammation of the eye, Varicella-zoster virus acute retinal necrosis, Watery itchy eyesAcne pustular, Allergic Contact Dermatitis, Allergy Skin, Atopic Dermatitis (AD), Atopic Dermatitis (AD) of the external ear canal, Bacterial diarrhoea, Burns, Carbuncle, Cradle Cap, Dermatitis, Dermatitis, Contact, Dermatitis, Eczematous, Diarrhoea, Discoid Lupus Erythematosus (DLE), Ear infection bacterial, Ear infection bacterial caused by susceptible bacteria, Gastrointestinal Infections, Hepatic coma, Hidradenitis Suppurativa (HS), Hot Water Burns (Scalds), Impetigo, Impetigo contagious, Infantile Eczema, Infected Wounds, Infected skin ulcer, Infection of the outer ear caused by susceptible bacteria, Infectious diarrhea, Inflammatory Reaction caused by Acne, Intertrigo, Itching caused by Infection, Lichen Planus (LP), Localized Infection caused by susceptible bacteria, Nail infection, Neurodermatitis, Otitis Externa, Postoperative Wound Infection, Psoriasis Vulgaris (Plaque Psoriasis), Pustular Dermatosis, Radiodermatitis, Secondarily Infected Eczema, Secondary Bacterial Infection, Skin Burns, Skin Infections, Skin Infections, Bacterial, Skin Irritation, Skin Ulcer, Solar erythema, Abrasions, Blistering caused by Staphylococcus, Erythematous eruptions, Intertriginous erythema of the anogenital, Ocular bacterial infections caused by susceptible bacteria, Resistant to other corticosteroids Dermatosis, Susceptible Bacterial InfectionsAcute Otitis Media, Bacteremia caused by Enterobacter aerogenes, Bacterial Conjunctivitis, Bacterial Infections, Chronic Otitis Media, Escherichia urinary tract infection, Klebsiella bacteraemia, Meningitis caused by Haemophilus influenzae, Meningitis, Bacterial, Ocular Inflammation, Otitis Externa, Otorrhoea, Superficial ocular infections of the conjunctiva caused by susceptible bacteria, Superficial ocular infections of the cornea caused by susceptible bacteria, Urinary Tract Infection, Ocular bacterial infections

How Ophth-neodex works

The short term effects of corticosteroids are decreased vasodilation and permeability of capillaries, as well as decreased leukocyte migration to sites of inflammation. Corticosteroids binding to the glucocorticoid receptor mediates changes in gene expression that lead to multiple downstream effects over hours to days.

Glucocorticoids inhibit neutrophil apoptosis and demargination; they inhibit phospholipase A2, which decreases the formation of arachidonic acid derivatives; they inhibit NF-Kappa B and other inflammatory transcription factors; they promote anti-inflammatory genes like interleukin-10.

Lower doses of corticosteroids provide an anti-inflammatory effect, while higher doses are immunosuppressive. High doses of glucocorticoids for an extended period bind to the mineralocorticoid receptor, raising sodium levels and decreasing potassium levels.

Like other aminoglycoside antibiotic drugs, neomycin inhibits bacterial ribosomes by binding to the 30S ribosomal subunit of susceptible bacteria and disrupting the translational machinery of bacterial protein synthesis. Bacterial translation is normally initiated by the mRNA binding to the 30S ribosomal subunit and subsequent binding with 50S subunit for elongation.

The alpha and gamma diaminobutyric acid of a positively charged polymyxin B forms an electrostatic interaction with the phosphate groups of a negatively charged lipid A on the outer membrane of a Gram negative bacterium. Calcium and Magnesium ions are displaced from phosphates of the membrane lipids, destabalising the lipopolysaccharide (LPS), increasing membrane permeability, causing cytoplasmic leaking, and killing the cell.

Polymyxin B can also bind and neutralize LPS released during bacterial lysis, preventing reactions to endotoxin.

A third activity of polymyxin B is the inhibition of type II NADH-quinone oxidoreductases in the bacterial inner membrane, which are essential for respiration.

Polymyxin is active against common Gram negative bacteria but not Gram negative cocci, Gram positive bacteria, or anaerobic bacteria.

Dosage

Ophth-neodex dosage

Intraarticular-

Inflammatory joint diseases:

• Adult: 0.8-4 mg depending on the size of the affected joint. For soft-tissue inj, 2-6 mg may be used. May repeat inj every 3-5 days to every 2-3 wk.

Intravenous-

Prophylaxis of nausea and vomiting associated with cytotoxic therapy:

• Adult: Prevention: 10-20 mg 15-30 minutes before admin of chemotherapy on each treatment day. For continuous infusion regimen: 10 mg every 12 hr on each treatment day. For midly emetogenic regimen: 4 mg every 4-6 hr.

Unresponsive shock:

• Adult: As phosphate: Initially, 40 mg or 1-6 mg/kg as a single IV inj, may repeat every 2-6 hr. Continue high-dose treatment only until patient's condition has stabilised and not to be continued beyond 48-72 hr.

Bacterial meningitis:

• Adult: 0.15 mg/kg 4 times daily, to be given 10-20 min before or with the 1st dose of anti-infective treatment. Treatment should be given for the first 2-4 days of the anti-infective treatment.
• Child: As phosphate: 2 mth-18 yr: 150 mcg/kg every 6 hr for 4 days, starting before or with 1st dose of antibacterial treatment.

Cerebral oedema caused by malignancy:

• Adult: As phosphate: 10 mg IV followed by 4 mg IM every 6 hr until response is achieved, usually after 12-24 hr. May reduce dosage after 2-4 days then gradually discontinued over 5-7 days. In severe cases, an initial dose of 50 mg IV may be given on day 1, with 8 mg every 2 hr, reduced gradually over 7-13 days. Maintenance dose: 2 mg 2-3 times daily.
• Child: As phosphate: 35 kg: Initially 25 mg, then 4 mg every 2 hr for 3 days, then 4 mg every 4 hr for 1 day, then 4 mg every 6 hr for 4 days, then decrease by 2 mg daily. Doses are given via IV inj.

Oral-

Anti-inflammatory:

• Adult: 0.75-9 mg daily in 2-4 divided doses; may also be given via IM/IV admin.
• Child: 1 mth-18 yr: 10-100 mcg/kg daily in 1-2 divided doses via oral admin, adjusted according to response; up to 300 micrograms/kg daily may be used in emergency situations.

Screening test for Cushing's syndrome:

• Adult: 0.5 mg every 6 hr for 48 hr after determining baseline 24-hr urinary 17-hydroxycorticosteroid (17-OHCS) concentrations. During the second 24 hr of dexamethasone admin, urine is collected and analysed for 17-OHCS. Alternatively, after a baseline plasma cortisol determination, 1 mg may be given at 11 pm and plasma cortisol determined at 8 am the next morning. Plasma cortisol and urinary output of 17-OHCS are depressed after dexamethasone admin in normal individuals but remain at basal levels in patients with Cushing's syndrome.

Acute exacerbations in multiple sclerosis:

• Adult: 30 mg daily for 1 wk followed by 4-12 mg daily for 1 mth.
• Child: 1 mth-12 yr: 100-400 mcg/kg daily in 1-2 divided doses; 12-18 yr: Initially 0.5-24 mg daily. Max. 24 mg daily.

Intravenous: Dissolve Polymyxin B 500,000 units in 300 to 500 ml solutions for parenteral Dextrose injection 5% for continuous drip.

Intramuscular: Dissolve Polymyxin B 500,000 units in 2 ml 0.9% Sodium Chloride solution. It is not recommended routinely because of severe pain at injection site, particularly in infants and children.

Intrathecal: Dissolve Polymyxin B 500,000 units in 10 ml 0.9% Sodium Chloride solution for 50,000 units per ml dosage unit.

In meningeal infections, Polymyxin B Sulfate should be administered only by the intrathecal route.

For IV route:

• Adult & Children (Normal kidney function): Dose (Units/kg/day) is 15,000-25,000(Not exceed 25,000) and Dosage frequency/Duration is infusions may be given every 12 hours over a period of approximately 60 to 90 minutes.
• Adult & Children (Renal impairment): Dose (Units/kg/day) is Less than 15,000 and Dosage frequency/Duration is Infusions may be given every 12 hours over a period of approximately 60 to 90 minutes.
• Infants (Normal kidney function): Dose (Units/kg/day) is Maximum 40,000

• Adult & Children: Dose (Units/kg/day) is 25,000-30,000 and Dosage frequency/Duration is Dose should be reduced in the presence of renal impairment. The dosage may be divided and given at either 4 or 6 hour intervals.
• Infants (Normal kidney function): Dose (Units/kg/day) is Maximum 40,000

• Children under 2 years of age: Dosage frequency/Duration is 20,000 units once daily, intrathecally for 3 to 4 days or 25,000 units once every other day. Continue with a dose of 25,000 units once every other day for at least 2 weeks after cultures of the cerebrospinal fluid are negative and sugar content has returned to normal.
• Adults and children over 2 years of age: 50,000 units once daily for 3 to 4 days, then 50,000 units once every other day for at least 2 weeks after cultures of the cerebrospinal fluid are negative and sugar content has returned to normal.

Side Effects

Dexamethasone is generally well tolerated in standard low doses, Nausea, vomiting, increased appetite, and obesity may occur. Higher doses may result behavioral personality changes. Following adverse reactions have been associate with prolonged systemic glucocorticoid therapy, endocrine & metabolic disturbances, fluid & electrolyte disturbances, musculo-skeletal effects like osteoporosis etc; GI effects like ulcer, bleeding, perforation; Opthelmic effects like Glaucoma, increased intraocular pressure etc; immunosuppressive effects like increased susceptibility to infection etc.

Clostridium difficile associated diarrhea has been reported with use of Polymyxin B. Nephrotixic reactions: Albuminuria, cylinduria, azotemia, and rising blood levels, Neurotoxic reactions: Facial flushing, dizziness progressing to ataxia, drowsiness, peripheral aresthesias (circumoral and stocking glove), apnea due to concurrent use of curariform muscle relaxants, other neurotoxic drugs or inadvertent overdosage, and signs of meningeal irritation with intrathecal administration, e.g., fever, headache, stiff neck. Other reactions occasionally reported: Drug fever, urticaria rash, severe pain at IM injections sites and thrombophelbitis at IV injections sites.

Toxicity

The oral LD₅₀ in female mice was 6.5g/kg and 794mg/kg via the intravenous route.

Overdoses are not expected with otic formulations. Chronic high doses of glucocorticoids can lead to the development of cataract, glaucoma, hypertension, water retention, hyperlipidemia, peptic ulcer, pancreatitis, myopathy, osteoporosis, mood changes, psychosis, dermal atrophy, allergy, acne, hypertrichosis, immune suppression, decreased resistance to infection, moon face, hyperglycemia, hypocalcemia, hypophosphatemia, metabolic acidosis, growth suppression, and secondary adrenal insufficiency. Overdose may be treated by adjusting the dose or stopping the corticosteroid as well as initiating symptomatic and supportive treatment.

The oral LD₅₀ of neomycin sulfate in mouse is > 8 g/kg. The subcutaneous LD₅₀ is 200 mg/kg in rat and 190 mg/kg in mouse. The intraperitoneal LD₅₀ in mouse is 305 mg/kg. The oral Lowest published toxic dose (TDLo) in woman is 12600 mg/kg/7D.

Because of low absorption, acute overdosage from oral neomycin is not likely to occur. However, prolonged administration of neomycin should be avoided because of the possibility of some systemic absorption and the risk of neurotoxicity, ototoxicity, and/or nephrotoxicity. Hemodialysis will remove neomycin from the blood. While nephrotoxicity and ototoxicity have been reported in otherwise patients without compromised renal function, the risk for developing these toxicities is increased in patients with renal impairment. Like other aminoglycosides, neomycin may cause fetal harm and total irreversible bilateral congenital deafness when administered in pregnant women.

Nephrotoxicity can occur in patients as polymyxin B is thought to accumulate in renal cells after renal tubular reabsorption. This accumulation can lead to apoptosis of renal cells and decrease in renal function. In recent studies, acute kidney injury (AKI) has been seen in 31.3% to 39.4% of patients receiving polymyxin B.

Overdose cases can cause neuromuscular block leading to apnea, muscular weakness, vertigo, transient facial parasthesia, slurred speed, vasomotor instability, visual disturbance, confusion, psychosis, and respiratory arrest. Renal failure has also been seen through decreased urine output, and increased serum concentrations of blood urea nitrogen.

Overdose of polymyxin B is treated by stopping the drug and beginning symptomatic treatment. Intravenous administration of mannitol may enhance renal clearance, and hemodialysis may manage renal complications.

Safety of polymyxin B has not been established in pregnancy, breast feeding, pediatrics, and geriatrics. Polymyxin B should no be used in pregnancy unless the benefit outweighs the risk. Nursing mothers should either stop nursing or stop polymyxin B treatment depending on the risks to both the mother and child. Pediatric patients should be frequently monitored for renal function and no dosing information is available in children under 2 years of age. Geriatric patients should have renal function assessed before and regularly during therapy.

Precaution

The lowest possible dose of corticosteroids should be used to control the conditions under treatment. Dexamethasone should be used with caution in patient with cardiomyopathy, heart failure, hypertension, or renal insufficiency, drug induced secondary adrenocortical insufficiency, peptic ulcer, diverticulitis, intestinal anastomosis, ulcerative colitis, osteoporosis, & latent tuberculosis etc.

Baseline renal function should be done prior to therapy, with frequent monitoring of renal function and blood levels of the drug during parenteral therapy.

Interaction

Drug interaction can be occurred with following drugs:Diuretics, cardiac glycosides, antidiabetics, NSAIDs, anticoagulants, antacids etc. Besides, if patients undergo long-term therapy of glucororticoids with concomitant salicylates, any reduction in glucocorticoid dosage should be made with caution, since salicylate intoxication has been reported in such cases.

The concurrent or sequential use of other neurotoxic and/or nephrotox-ic drugs with Polymyxin B sulfate, particularly bacitracin, kanamycin, streptomycin, tobramycin, amikacin, cephaloridine, cephalothin, paromycin, polymyxin E (colistin), neomycin, gentamicin, and vancomycin, Bumetanide, celecoxib, cisplatin, cyclosporine, diclofenac, misoprostol, diphenhydramine, ibuprofen, naproxen, esomeprazole, etodolac, general anesthetic, gentamycin, ketorolac, meloxicam, tenofovir etc should be avoided.

Volume of Distribution

A 1.5mg oral dose of dexamethasone has a volume of distribution of 51.0L, while a 3mg intramuscular dose has a volume of distribution of 96.0L.

The small fraction of absorbed neomycin is rapidly distributed in the tissues. The amount of systemically absorbed neomycin is reported to increase cumulatively with each repeated dose administered until a steady state is reached.

1 compartment models estimate the volume of distribution to be 34.3L to 47.2L. However, the general consensus is that the volume of distribution is yet to be determined.

Elimination Route

Absorption via the intramuscular route is slower than via the intravenous route. A 3mg intramuscular dose reaches a C_max of 34.6±6.0ng/mL with a T_max of 2.0±1.2h and an AUC of 113±38ng*h/mL. A 1.5mg oral dose reaches a C_max of 13.9±6.8ng/mL with a T_max of 2.0±0.5h and an AUC of 331±50ng*h/mL. Oral dexamethasone is approximately 70-78% bioavailable in healthy subjects.

Neomycin is poorly absorbed from the gastrointestinal tract. Gastrointestinal absorption of the drug may be increased if inflammatory or ulcerative gastrointestinal disease is present.

Administration by the oral route does not lead to absorption.

Half Life

The mean terminal half life of a 20mg oral tablet is 4 hours. A 1.5mg oral dose of dexamethasone has a half life of 6.6±4.3h, while a 3mg intramuscular dose has a half life of 4.2±1.2h.

There is limited information on the half-life of neomycin.

In one study the half life was 9 to 11.5 hours. However, a Canadian monograph states the half life to be 6 hours, and 48-72 hours in patients with renal insufficiency.

Clearance

A 20mg oral tablet has a clearance of 15.7L/h. A 1.5mg oral dose of dexamethasone has a clearance of 15.6±4.9L/h while a 3.0mg intramuscular dose has a clearance of 9.9±1.4L/h.

There is limited information on the clearance rate of neomycin.

1 compartment models estimate clearance to be 2.37L/h to 2.5L/h.

Elimination Route

Corticosteroids are generally eliminated predominantly in the urine. However, dexamethasone is 15

The small absorbed fraction of neomycin is excreted by the kidney. The unabsorbed portion of the drug is excreted unchanged in the feces.

Polymyxin B is proposed to be primarily eliminated through renal tubular reabsorption and non-renal pathways. Urine collection in humans and animals show 1. However, a Canadian product monograph states the drug is primarily eliminated through the kidneys and that 60% of polymyxin B is recovered in the urine. This discrepancy can be explained by the 12 to 24 hour lag time between administration and significant elimination of polymyxin B. Non-renal elimination is not well understood but all 4 components of polymyxin B have been detected in bile.

Pregnancy & Breastfeeding use

Pregnancy Category C. There are no adequate and well-controlled studies in pregnant women. Corticosteroids should be used during pregnancy only if the potential benefit justifies. Glucocorticoids appear in breast milk, Mothers taking high dosages of corticosteroids should be advised not to breast-feed.

There are no controlled data in human pregnancy. Safety has not been established during pregnancy. There is no recommendation regarding use during lactation. There is no study on whether it is secreted with human milk.

Contraindication

In case of adrenal insufficiency, no absolute contraindications are applicable. In the treatment of non endocrine diseases where pharmacological doses are more likely to be used, the contraindications have to be considered carefully.

Relative contraindications include the followings: patient with Cushing’s syndrome, Osteoporosis, Diabetes mellitus, renal insufficiency, gastrointestinal ulcers, systemic fungal infection & acute infection.

Acute Overdose

Overdose is unlikely; however, treatment of overdose is by supportive and symptomatic therapy.

Polymyxin-induced toxicity associated with overdose has been reported. Overdose of Polymyxin can result in neuromuscular blockade, which can lead to apnea, muscular weakness, vertigo, transient facial paresthesia, slurred speech, vasomotor instability, visual disturbance, confusion, psychosis and possible respiratory arrest. Overdose can also cause renal failure characterized by decreased urine output and increased serum concentrations of BUN and creatinine. There is no specific antidote for Polymyxin B Sulfate overdose. In case of Polymyxin B Sulfate overdose, the drug should be stopped and symptomatic treatment instituted. Quick diuresis by IV administered mannitol may help to enhance renal clearance of the drug and thus to reduce serum drug levels. Hemodialysis or peritoneal dialysis may help in order to manage renal complications.

Storage Condition

Store at 15-30° C.

Before reconstitution, do not store above 30°C; and keep away from light and out of the reach of children. After reconstitution or dilution, unused portion must be stored at 2° to 8°C and should be discarded after 72 hours if not used.

Innovators Monograph

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