DRUGS & SUPPLEMENTS

Inflobid-D

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Inflobid-D uses

Inflobid-D consists of Dexamethasone, Ofloxacin, Sodium Phosphate.

Dexamethasone:


Pharmacological action

Inflobid-D is a glucocorticosteroid. This medication Inhibits the function of leukocytes and tissue macrophages. Inflobid-D (Dexamethasone) restricts the migration of leukocytes in the area of inflammation. This drug violates the ability of macrophages to phagocytosis and the formation of interleukin-1. Inflobid-D (Dexamethasone) decreases capillary permeability caused by histamine release. This medicine inhibits the activity of fibroblasts and collagen formation.

Inflobid-D (Dexamethasone) inhibits the activity of phospholipase A2, which leads to suppression of the synthesis of prostaglandins and leukotrienes.

With direct application to the vessels this drug has a vasoconstrictor effect.

Inflobid-D (Dexamethasone) has a pronounced dose-dependent effect on the metabolism of carbohydrates, proteins and fats.

In high doses Inflobid-D (Dexamethasone) may increase the excitability of brain tissue and contributes to lowering the threshold of convulsive readiness.

With systemic use of therapeutic activity of Inflobid-D (Dexamethasone) is due to anti-inflammatory, antiallergic, immunosuppressive and antiproliferative action.

For external and local use of therapeutic activity of Inflobid-D (Dexamethasone) is due to anti-inflammatory, antiallergic and antiexudative (due to vasoconstrictor effect) effect.

Pharmacokinetics

The plasma protein binding is 60-70%. This medication penetrates histohematic barriers. In a small amount it is excreted in breast milk. Inflobid-D (Dexamethasone) metabolized in a liver. T1/2 is 2-3 hours. This drug is excreted by kidneys.

When Inflobid-D (Dexamethasone) applied topically in ophthalmology it absorbed through the cornea with intact epithelium in moisture anterior chamber. When inflammation of the tissues of the eye or mucosal damage and corneal absorption rate of Inflobid-D (Dexamethasone) significantly increased.

Why is Inflobid-D prescribed?

For oral administration: Biermer's disease; acute and subacute thyroiditis, hypothyroidism, progressive ophthalmopathy associated with thyrotoxicosis; bronchial asthma; rheumatoid arthritis in the acute phase; ulcerative colitis; connective tissue disease; autoimmune hemolytic anemia, thrombocytopenia, aplasia and hypoplasia of hematopoiesis, agranulocytosis, serum sickness; acute erythroderma, pemphigus (normal), acute eczema (early treatment); malignant tumor (as a palliative therapy); congenital adrenogenital syndrome; cerebral edema (usually after a preliminary parenteral corticosteroids).

For parenteral administration: shock of various origins; swelling of the brain (with brain tumors, head injury, neurosurgical intervention, brain hemorrhage, encephalitis, meningitis, radiation damage); asthmatic status; severe allergic reactions (angioedema, bronchospasm, dermatosis, acute anaphylactic reaction to medication, transfusion serum, pyrogenic reactions); acute hemolytic anemia, thrombocytopenia, acute lymphoblastic leukemia, agranulocytosis; serious infectious diseases (in combination with antibiotics); acute adrenal insufficiency, acute croup; arthropathy (scapulohumeral periarthritis, epicondylitis, styloiditis, bursitis, tenosynovitis, compression neuropathy, osteochondrosis, arthritis of various etiologies, osteoarthritis).

For use in ophthalmic practice: not purulent and allergic conjunctivitis, keratitis, keratoconjunctivitis without damaging the epithelium, iritis, iridocyclitis, blefaroconjuntivitis, blepharitis, episcleritis, scleritis, inflammation of injuries and eye surgeries, sympathetic ophthalmia.

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Dosage and administration

The dosing regimen is individual. Orally for severe disease at the beginning of treatment it is prescribed to 10-15 mg / day, maintenance dose may be 2-4.5 mg / day or more. The daily dose divided into 2-3 doses. In small doses Inflobid-D is taken 1 time in the morning.

For parenteral administration this medication is administered IV slowly bolus or infusion (acute and urgent conditions); IM; it is possible also periarticular and intraarticular injection. During the day it can be administered from 4 to 20 mg of Inflobid-D (Dexamethasone) 3-4 times / day. The duration of parenteral administration is usually 3-4 days, then move on to maintenance therapy of oral form. In the acute period in various diseases and early treatment Inflobid-D (Dexamethasone) used in higher doses. Upon reaching the effect the dose is decreased within a few days before reaching the maintenance dose or until discontinuation of treatment.

When used in ophthalmology for acute conditions this drug instilled into conjunctival sac 1-2 drops every 1-2 hours, then with a decrease in inflammation after every 4-6 hours. The duration of treatment is from 1-2 days to several weeks depending on the clinical course of disease.

Inflobid-D (Dexamethasone) side effects, adverse reactions

Endocrine system: impaired glucose tolerance, steroid diabetes mellitus or manifestation of latent diabetes mellitus, suppression of adrenal function, Itsenko-Cushing syndrome (including moon face, obesity, pituitary type, hirsutism, increased blood pressure, dysmenorrhea, amenorrhea, myasthenia gravis, striae), delayed sexual development in children.

Metabolism: increased excretion of calcium, hypocalcemia, weight gain, negative nitrogen balance (increased protein breakdown), increased sweating, hypernatremia, hypokalemia.

CNS: delirium, disorientation, euphoria, hallucinations, manic-depressive psychosis, depression, paranoia, increased intracranial pressure, nervousness or anxiety, insomnia, dizziness, vertigo, pseudotumor cerebellum, headache, convulsions.

Cardio-vascular system: arrhythmia, bradycardia (up to cardiac arrest); development (in predisposed patients) or increased severity of chronic heart failure, ECG changes typical of hypokalemia, increased blood pressure, hypercoagulability, thrombosis. In patients with acute and subacute myocardial infarction - spread necrosis, slowing the formation of scar tissue that can lead to rupture of the heart muscle; with intracranial introduction - nosebleeds.

Digestive system: nausea, vomiting, pancreatitis, steroid gastric and duodenal ulcers, erosive esophagitis, bleeding and perforation of the gastrointestinal tract, increase or decrease in appetite, flatulence, hiccups; rarely - increased activity of hepatic transaminases and alkaline phosphatase.

Sensory organs: posterior subcapsular cataracts, increased intraocular pressure with possible damage to the optic nerve, propensity to develop secondary bacterial, fungal or viral infections of the eye, trophic changes of the cornea, exophthalmos.

Musculoskeletal system: growth retardation and ossification processes in children (premature closure of epiphyseal growth zones), osteoporosis (very rare - a pathological bone fractures, aseptic necrosis of head of humerus and femur), rupture of tendons of muscles, steroid myopathy, reduced muscle mass (atrophy).

Dermatological reactions: delayed wound healing, petechiae, ecchymosis, skin thinning, hyper or hypopigmentation, steroid acne, stretch marks, susceptibility to the development of pyoderma and candidiasis.

Allergic reactions: generalized (including skin rash, itching, anaphylactic shock) and when applied topically.

Effects associated with immunosuppressive action: development or worsening of infection (the appearance of this side effect contribute jointly used immunosuppressive drugs, and vaccinations).

Local reactions: when Inflobid-D (Dexamethasone) administered parenteral - tissue necrosis.

For external use: rarely - itching, redness, burning, dryness, folliculitis, acne, hypopigmentation, perioral dermatitis, allergic dermatitis, maceration of the skin, secondary infection, skin atrophy, striae, miliaria. With prolonged use or application to large areas of skin may develop systemic side effects characteristic of SCS.

Inflobid-D contraindications

For short-term use for health reasons - increased sensitivity to Inflobid-D (Dexamethasone).

For intra-articular injection and injection directly into the lesion: previous arthroplasty, abnormal bleeding (endogenous or caused by the use of anticoagulants), intra-articular fracture, infection (sepsis) inflammation in the joints and periarticular infections (including in history), as well as general infectious disease, pronounced juxta-articular osteoporosis, no signs of inflammation in the joints ("dry" joint, such as osteoarthritis without synovitis), severe bone destruction and deformity of the joint (a sharp narrowing of joint space, ankylosis), instability of the joint as a result of arthritis, aseptic necrosis of the epiphyses of bones forming the joint.

For external use: bacterial, viral, fungal skin diseases, tuberculosis, skin, cutaneous manifestations of syphilis, skin tumors, post-vaccination period, violation of the integrity of the skin (ulcers, wounds), children's age (up to 2 years, with itching in the anal area - up to 12 years), rosacea, acne vulgaris, perioral dermatitis.

For use in ophthalmology: bacterial, viral, fungal eye diseases, tuberculosis eye damage, tampering with the ocular epithelium, acute form of purulent eye infection in the absence of specific therapy, diseases of the cornea, combined with defects in the epithelium, trachoma, glaucoma.

Using during pregnancy and breastfeeding

During pregnancy and lactating Inflobid-D (Dexamethasone) is used taking into account the expected therapeutic effect and adverse effect on the fetus. Long-term therapy during pregnancy does not exclude the possibility of violations of fetal growth. In the case of the end of pregnancy there is a danger of atrophy of the adrenal cortex of the fetus, which may require replacement therapy in the newborn.

Category effects on the fetus by FDA - C.

Inflobid-D (Dexamethasone) in case of emergency / overdose

Symptoms: increased side effects.

Treatment: the development of adverse reactions - symptomatic therapy, the Itsenko-Cushing syndrome - the prescription of aminoglutethimide.

Ofloxacin:


Pharmacological action

Inflobid-D is an antimicrobial agents of broad-spectrum action type from fluoroquinolone group. Bactericidal action of Inflobid-D (Ofloxacin) is due to blockage of the enzyme DNA gyrase in bacterial cells. This medication is highly active against most of gram-negative bacteria: Escherichia coli, Salmonella spp., Shigella spp., Proteus spp., Morganella morganii, Klebsiella spp. (including Klebsiella pneumoniae), Enterobacter spp., Serratia spp., Citrobacter spp., Yersinia spp., Providencia spp., Haemophilus influenzae, Neisseria gonorrhoeae, Neisseria meningitidis, Mycoplasma spp., Legionella pneumophila, Acinetobacter spp., and Chlamydia spp.

Inflobid-D (Ofloxacin) is active against some gram-positive bacteria (including Staphylococcus spp., Streptococcus spp., especially beta-hemolytic streptococci).

Enterococcus faecalis, Streptococcus pneumoniae, Pseudomonas spp. are moderately susceptible to Inflobid-D (Ofloxacin).

Anaerobic bacteria (except Bacteroides ureolyticus) are insensitive to Inflobid-D (Ofloxacin).

This drug is resistant to beta-lactamases.

Pharmacokinetics

After oral administration Inflobid-D (Ofloxacin) is rapidly and completely absorbed from the gastrointestinal tract. Ingestion has a little effect on the extent of absorption but may slow its speed. Cmax plasma levels reached in 2 hours.

The protein binding is 25%. Inflobid-D (Ofloxacin) is widely distributed in tissues and body fluids (organs of urinary system, reproductive organs, prostate, lung, ENT organs, gall bladder, bone, skin).This medicine is excreted in the urine in unchanged form (about 80% in 24 h). A small portion of the active substance (4%) is excreted in the feces. T1/2 is 6 h.

Why is Inflobid-D prescribed?

Infectious-inflammatory diseases caused by microorganisms sensitive to Inflobid-D (Ofloxacin), including: diseases of the lower respiratory tract, ear, nose, throat, skin, soft tissues, bones, joints, infectious and inflammatory diseases of the abdominal organs (except bacterial enteritis) and pelvic infection, kidney and urinary tract, prostatitis, gonorrhea.

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Dosage and administration

Dosing regimen of Inflobid-D is individual. Daily dose of 200-800 mg, the multiplicity of application 2 times / day. For patients with impaired renal function (creatinine clearance 20-50 ml / min), the first dose is 200 mg, then 100 mg every 24 hours. When CC is less than 20 ml / min, the first dose is 200 mg, then 100 mg every 48 hours.

Inflobid-D (Ofloxacin) side effects, adverse reactions

Digestive system: nausea, vomiting, diarrhea, abdominal pain and cramps, appetite loss, dry mouth, flatulence, gastrointestinal dysfunction, constipation; rarely - liver damage, liver necrosis, jaundice, hepatitis, intestinal perforation, pseudomembranous colitis, bleeding from the gastrointestinal tract, disorders of the oral mucosa, heartburn, elevated liver enzymes, including GGT and LDH, increased serum bilirubin.

CNS and peripheral nervous system: insomnia, dizziness, fatigue, drowsiness, nervousness; rarely - convulsions, anxiety, cognitive changes, depression, abnormal dreams, euphoria, hallucinations, paresthesia, syncope, tremor, confusion, nystagmus, suicidal thoughts or attempts, disorientation, psychotic reactions, paranoia, phobia, agitation, aggressiveness, emotional instability, peripheral neuropathy, ataxia, incoordination, exacerbation of extrapyramidal disorders, speech disorder.

Allergic reactions: skin rash, itching, rarely - angioedema, urticaria, vasculitis, allergic pneumonitis, anaphylactic shock, erythema multiforme, Stevens-Johnson syndrome, erythema nodosum, exfoliative dermatitis, toxic epidermal necrolysis, conjunctivitis.

Sexual system: an itch on the external genitalia in women, vaginitis, vaginal discharge; rare - burning, irritation, pain and rash in the genital area of women, dysmenorrhea, menorrhagia, metrorrhagia, vaginal candidiasis.

Cardiovascular system: rarely - heart failure, edema, hypertension, hypotension, palpitation, vasodilatation, cerebral thrombosis, pulmonary edema, and tachycardia.

Urinary system: rarely - dysuria, urinary frequency, urinary retention, anuria, polyuria formation of kidney stones, kidney failure, nephritis, hematuria, albuminuria, candiduria.

Musculoskeletal system: rarely - arthralgia, myalgia, tendonitis, muscle weakness, exacerbation of myasthenia gravis.

Metabolism: rarely - thirst, weight loss, hyper- or hypoglycemia (especially in patients with diabetes mellitus receiving insulin or oral hypoglycemic agents), acidosis, increase in serum triglycerides, cholesterol, potassium.

Respiratory system: rarely - cough, runny nose, respiratory failure, dyspnea, bronchospasm, stridor.

Sensory organs: rarely - hearing loss, tinnit, diplopia, nystagmus, impaired clarity of vision, disturbances of taste, smell, photophobia.

Dermatological reactions: rarely - photosensitivity, hyperpigmentation, vesicle-bullous eruption.

Hematopoietic system: rarely - anemia, hemorrhage, pancytopenia, agranulocytosis, leukopenia, reversible suppression of bone marrow hematopoiesis, thrombocytopenia, thrombocytopenic purpura, petechiae, ecchymosis, increased prothrombin time.

Other: chest pain, sore throat, fever, body aches, rarely - fatigue, chills, malaise, epistaxis, increased sweating.

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Inflobid-D contraindications

Pregnancy, lactation, childhood and adolescence to 18 years, increased sensitivity to Inflobid-D (Ofloxacin) or other quinolone derivatives.

Using during pregnancy and breastfeeding

Inflobid-D is contraindicated during pregnancy and lactation.

Category effects on the fetus by FDA - C.

Special instructions

Use with caution in patients with impaired renal function and liver.

During the period of treatment required to conduct monitoring of blood glucose. Long-term therapy is necessary to periodically monitor the kidney function, liver and peripheral blood picture.

When using Inflobid-D (Ofloxacin) it should be ensure adequate hydration of the body, the patient should be subjected to ultraviolet irradiation.

In experimental studies the mutagenic potential was not been identified. Long-term studies to determine the carcinogenicity of Inflobid-D (Ofloxacin) were not conducted.

Safety and efficacy in children and adolescents under the age of 18 is not defined.

Use with caution in patients whose activities are connected with the necessity of high concentration of attention and quickness of psychomotor reactions.

Inflobid-D drug interactions

Simultaneous administration of Inflobid-D (Ofloxacin) with:

  • antacids containing calcium, magnesium or aluminum, with sucralfate, with preparations containing two-and trivalent cations, such as iron, or multivitamins containing zinc it may be in breach absorption of quinolones, resulting in a decrease in their concentration in the body. These medications should not be used for 2 hours before or within 2 hours after taking Inflobid-D (Ofloxacin).
  • NSAIDs increases the risk of stimulating effect on the central nervous system and seizures.
  • theophylline may increase its concentration in blood plasma (including the equilibrium state), increasing half-life. This increases the risk of adverse reactions associated with the action of theophylline.
  • beta-lactam antibiotics, aminoglycosides and metronidazole there were observed additive interaction.

    Inflobid-D in case of emergency / overdose

    Symptoms: drowsiness, nausea, vomiting, dizziness, disorientation, lethargy, confusion.

    Treatment: gastric lavage, maintenance of vital functions.

  • Sodium Phosphate:


    1 INDICATIONS AND USAGE

    Inflobid-D nitrite is indicated for sequential use with Inflobid-D (Sodium Phosphate) thiosulfate for treatment of acute cyanide poisoning that is judged to be life-threatening. (1)

    • Use with caution if the diagnosis of cyanide poisoning is uncertain. (1)

    1.1 Indication

    Inflobid-D (Sodium Phosphate) Nitrite Injection is indicated for sequential use with Inflobid-D (Sodium Phosphate) thiosulfate for the treatment of acute cyanide poisoning that is judged to be life-threatening. When the diagnosis of cyanide poisoning is uncertain, the potentially life-threatening risks associated with Inflobid-D (Sodium Phosphate) Nitrite Injection should be carefully weighed against the potential benefits, especially if the patient is not in extremis.

    1.2 Identifying Patients with Cyanide Poisoning

    Cyanide poisoning may result from inhalation, ingestion, or dermal exposure to various cyanide-containing compounds, including smoke from closed-space fires. Sources of cyanide poisoning include hydrogen cyanide and its salts, cyanogenic plants, aliphatic nitriles, and prolonged exposure to Inflobid-D nitroprusside.

    The presence and extent of cyanide poisoning are often initially unknown. There is no widely available, rapid, confirmatory cyanide blood test. Treatment decisions must be made on the basis of clinical history and signs and symptoms of cyanide intoxication. If clinical suspicion of cyanide poisoning is high, Inflobid-D (Sodium Phosphate) Nitrite Injection and Inflobid-D (Sodium Phosphate) Thiosulfate Injection should be administered without delay.

    Symptoms Signs
    • Headache
    • Confusion
    • Dyspnea
    • Chest Tightness
    • Nausea
    • Altered Mental Status

      (e.g., confusion, disorientation)

    • Seizures or Coma
    • Mydriasis
    • Tachypnea/Hyperpnea (early)
    • Bradypnea/Apnea (late)
    • Hypertension (early)/ Hypotension (late)
    • Cardiovascular Collapse
    • Vomiting
    • Plasma Lactate Concentration ≥ 8 mmol/L

    In some settings, panic symptoms including tachypnea and vomiting may mimic early cyanide poisoning signs. The presence of altered mental status (e.g., confusion and disorientation) and/or mydriasis is suggestive of true cyanide poisoning although these signs can occur with other toxic exposures as well.

    The expert advice of a regional poison control center may be obtained by calling 1-800-222-1222.

    Smoke Inhalation

    Not all smoke inhalation victims will have cyanide poisoning and may present with burns, trauma, and exposure to other toxic substances making a diagnosis of cyanide poisoning particularly difficult. Prior to administration of Inflobid-D (Sodium Phosphate) Nitrite Injection, smoke-inhalation victims should be assessed for the following:

    • Exposure to fire or smoke in an enclosed area
    • Presence of soot around the mouth, nose, or oropharynx
    • Altered mental status

    Although hypotension is highly suggestive of cyanide poisoning, it is only present in a small percentage of cyanide-poisoned smoke inhalation victims. Also indicative of cyanide poisoning is a plasma lactate concentration greater than or equal to 10 mmol/L (a value higher than that typically listed in the table of signs and symptoms of isolated cyanide poisoning because carbon monoxide associated with smoke inhalation also contributes to lactic acidemia). If cyanide poisoning is suspected, treatment should not be delayed to obtain a plasma lactate concentration.

    1.3 Use with Other Cyanide Antidotes

    Caution should be exercised when administering cyanide antidotes, other than Inflobid-D (Sodium Phosphate) thiosulfate, simultaneously with Inflobid-D (Sodium Phosphate) Nitrite Injection, as the safety of co-administration has not been established. If a decision is made to administer another cyanide antidote, other than Inflobid-D (Sodium Phosphate) thiosulfate, with Inflobid-D (Sodium Phosphate) Nitrite Injection, these drugs should not be administered concurrently in the same IV line. [see Dosage and Administration (2.2) ]

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    2 DOSAGE AND ADMINISTRATION

    Age Intravenous Dose of Inflobid-D Nitrite and Inflobid-D (Sodium Phosphate) Thiosulfate
    Adults
    • Inflobid-D (Sodium Phosphate) Nitrite -10 mL of Inflobid-D (Sodium Phosphate) nitrite at the rate of 2.5 to 5 mL/minute
    • Inflobid-D (Sodium Phosphate) Thiosulfate - 50 mL of Inflobid-D (Sodium Phosphate) thiosulfate immediately following administration of Inflobid-D (Sodium Phosphate) nitrite.
    Children
    • Inflobid-D (Sodium Phosphate) Nitrite - 0.2 mL/kg (6 mg/kg or 6-8 mL/m2 BSA) of Inflobid-D (Sodium Phosphate) nitrite at the rate of 2.5 to 5 mL/minute not to exceed 10 mL
    • Inflobid-D (Sodium Phosphate) Thiosulfate - 1 mL/kg of body weight (250 mg/kg or approximately 30-40 mL/m2 of BSA) not to exceed 50 mL total dose immediately following administration of Inflobid-D (Sodium Phosphate) nitrite.

    Redosing: If signs of cyanide poisoning reappear, repeat treatment using one-half the original dose of both Inflobid-D (Sodium Phosphate) nitrite and Inflobid-D (Sodium Phosphate) thiosulfate.

    Monitoring: Blood pressure must be monitored during treatment. (2.2)

    2.1 Administration Recommendation

    Comprehensive treatment of acute cyanide intoxication requires support of vital functions. Administration of Inflobid-D (Sodium Phosphate) nitrite, followed by Inflobid-D (Sodium Phosphate) thiosulfate, should be considered adjunctive to appropriate supportive therapies. Airway, ventilatory and circulatory support, and oxygen administration should not be delayed to administer Inflobid-D (Sodium Phosphate) nitrite and Inflobid-D (Sodium Phosphate) thiosulfate.

    Inflobid-D (Sodium Phosphate) nitrite injection and Inflobid-D (Sodium Phosphate) thiosulfate injection are administered by slow intravenous injection. They should be given as early as possible after a diagnosis of acute life-threatening cyanide poisoning has been established. Inflobid-D (Sodium Phosphate) nitrite should be administered first, followed immediately by Inflobid-D (Sodium Phosphate) thiosulfate. Blood pressure must be monitored during infusion in both adults and children. The rate of infusion should be decreased if significant hypotension is noted.

    Age Intravenous Dose of Inflobid-D (Sodium Phosphate) Nitrite and Inflobid-D (Sodium Phosphate) Thiosulfate
    Adults
    • Inflobid-D (Sodium Phosphate) Nitrite -10 mL of Inflobid-D (Sodium Phosphate) nitrite at the rate of 2.5 to 5 mL/minute
    • Inflobid-D (Sodium Phosphate) Thiosulfate - 50 mL of Inflobid-D (Sodium Phosphate) thiosulfate immediately following administration of Inflobid-D (Sodium Phosphate) nitrite.
    Children
    • Inflobid-D (Sodium Phosphate) Nitrite -0.2 mL/kg (6 mg/kg or 6-8 mL/m2 BSA) of Inflobid-D (Sodium Phosphate) nitrite at the rate of 2.5 to 5 mL/minute not to exceed 10 mL
    • Inflobid-D (Sodium Phosphate) Thiosulfate - 1 mL/kg of body weight (250 mg/kg or approximately 30-40 mL/m2 of BSA) not to exceed 50 mL total dose immediately following administration of Inflobid-D (Sodium Phosphate) nitrite.

    NOTE: If signs of poisoning reappear, repeat treatment using one-half the original dose of both Inflobid-D (Sodium Phosphate) nitrite and Inflobid-D (Sodium Phosphate) thiosulfate.

    In adult and pediatric patients with known anemia, it is recommended that the dosage of Inflobid-D (Sodium Phosphate) nitrite should be reduced proportionately to the hemoglobin concentration.

    All parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

    2.2 Recommended Monitoring

    Patients should be monitored for at least 24-48 hours after Inflobid-D Nitrite Injection administration for adequacy of oxygenation and perfusion and for recurrent signs and symptoms of cyanide toxicity. When possible, hemoglobin/hematocrit should be obtained when treatment is initiated. Measurements of oxygen saturation using standard pulse oximetry and calculated oxygen saturation values based on measured PO2 are unreliable in the presence of methemoglobinemia.

    Methemoglobin level: Administrations of Inflobid-D (Sodium Phosphate) nitrite solely to achieve an arbitrary level of methemoglobinemia may be unnecessary and potentially hazardous. The therapeutic effects of Inflobid-D (Sodium Phosphate) nitrite do not appear to be mediated by methemoglobin formation alone and clinical responses to Inflobid-D (Sodium Phosphate) nitrite administration have been reported in association with methemoglobin levels of less than 10%. Administration of Inflobid-D (Sodium Phosphate) nitrite beyond the initial dose should be guided primarily by clinical response to treatment (i.e., a second dose should be considered only if there is inadequate clinical response to the first dose). It is generally recommended that methemoglobin concentrations be closely monitored and kept below 30%. Serum methemoglobin levels should be monitored during treatment using co-oximetry, and administration of Inflobid-D (Sodium Phosphate) nitrite should generally be discontinued when methemoglobin levels exceed 30%. Intravenous methylene blue and exchange transfusion have been reported in the literature as treatments for life-threatening methemoglobinemia.

    2.3 Incompatibility Information

    Chemical incompatibility has been reported between Inflobid-D (Sodium Phosphate) nitrite and hydroxocobalamin and these drugs should not be administered simultaneously through the same IV line. No chemical incompatibility has been reported between Inflobid-D (Sodium Phosphate) thiosulfate and Inflobid-D (Sodium Phosphate) nitrite, when administered sequentially through the same IV line as described in Dosage and Administration.

    3 DOSAGE FORMS AND STRENGTHS

    Inflobid-D (Sodium Phosphate) Nitrite Injection consists of:

    • One vial of Inflobid-D (Sodium Phosphate) nitrite injection, USP 300 mg/10mL (30 mg/mL)

    Administration of the contents of one vial constitutes a single dose.

    • Injection, 300 mg/10 mL (30 mg/mL). (3)

    4 CONTRAINDICATIONS

    None

    • None. (4)

    5 WARNINGS AND PRECAUTIONS

    • Methemoglobinemia: Inflobid-D nitrite reacts with hemoglobin to form methemoglobin and should be used with caution in patients known to have anemia. Monitor oxyhemoglobin and methemoglobin levels by pulse oximetry or other measurements. Optimally, the Inflobid-D (Sodium Phosphate) nitrite dose should be reduced in proportion to the oxygen carrying capacity. (5.2)
    • Smoke inhalation: Carbon monoxide contained in smoke can result in the formation of carboxyhemoglobin that can reduce the oxygen carrying capacity of the blood. Inflobid-D (Sodium Phosphate) nitrite should be used with caution in patients with smoke inhalation injury because of the potential for worsening hypoxia due to methemoglobin formation. Carboxyhemoglobin and oxyhemoglobin levels should be monitored by pulse oximetry or other measurements in patients that present with evidence of smoke inhalation. Optimally, the Inflobid-D (Sodium Phosphate) nitrite dose should be reduced in proportion to the oxygen carrying capacity. (5.4)

    5.1 Hypotension

    5.2 Methemoglobinemia

    Supportive care alone may be sufficient treatment without administration of antidotes for many cases of cyanide intoxication, particularly in conscious patients without signs of severe toxicity. Patients should be closely monitored to ensure adequate perfusion and oxygenation during treatment with Inflobid-D nitrite.

    Methemoglobin levels should be monitored and oxygen administered during treatment with Inflobid-D (Sodium Phosphate) nitrite whenever possible. When Inflobid-D (Sodium Phosphate) nitrite is administered to humans a wide range of methemoglobin concentrations occur. Methemoglobin concentrations as high as 58% have been reported after two 300-mg doses of Inflobid-D (Sodium Phosphate) nitrite administered to an adult. Inflobid-D (Sodium Phosphate) nitrite should be used with caution in the presence of other drugs that may cause methemoglobinemia such as procaine and nitroprusside. Inflobid-D (Sodium Phosphate) nitrite should be used with caution in patients who may be particularly susceptible to injury from vasodilation and its related hemodynamic sequelae. Hemodynamics should be monitored closely during and after administration of Inflobid-D (Sodium Phosphate) nitrite, and infusion rates should be slowed if hypotension occurs.

    5.3 Anemia

    Inflobid-D (Sodium Phosphate) nitrite should be used with caution in patients with known anemia. Patients with anemia will form more methemoglobin (as a percentage of total hemoglobin) than persons with normal red blood cell (RBC) volumes. Optimally, these patients should receive a Inflobid-D (Sodium Phosphate) nitrite dose that is reduced in proportion to their oxygen carrying capacity.

    5.4 Smoke Inhalation Injury

    Inflobid-D nitrite should be used with caution in persons with smoke inhalation injury or carbon monoxide poisoning because of the potential for worsening hypoxia due to methemoglobin formation.

    5.5 Neonates and Infants

    Neonates and infants may be more susceptible than adults and older pediatric patients to severe methemoglobinemia when Inflobid-D (Sodium Phosphate) nitrite is administered. Reduced dosing guidelines should be followed in pediatric patients.

    5.6 G6PD Deficiency

    Because patients with G6PD deficiency are at increased risk of a hemolytic crisis with Inflobid-D nitrite administration, alternative therapeutic approaches should be considered in these patients. Patients with known or suspected G6PD deficiency should be monitored for an acute drop in hematocrit. Exchange transfusion may be needed for patients with G6PD deficiency who receive Inflobid-D (Sodium Phosphate) nitrite.

    5.7 Use with Other Drugs

    Inflobid-D (Sodium Phosphate) nitrite should be used with caution in the presence of concomitant antihypertensive medications, diuretics or volume depletion due to diuretics, or drugs known to increase vascular nitric oxide, such as PDE5 inhibitors.

    6 ADVERSE REACTIONS

    There have been no controlled clinical trials conducted to systematically assess the adverse events profile of Inflobid-D (Sodium Phosphate) nitrite.

    The medical literature has reported the following adverse events in association with Inflobid-D (Sodium Phosphate) nitrite administration. These adverse events were not reported in the context of controlled trials or with consistent monitoring and reporting methodologies for adverse events. Therefore, frequency of occurrence of these adverse events cannot be assessed.

    Cardiovascular system: syncope, hypotension, tachycardia, methemoglobinemia, palpitations, dysrhythmia

    Hematological: methemoglobinemia

    Central nervous system: headache, dizziness, blurred vision, seizures, confusion, coma

    Gastrointestinal system: nausea, vomiting, abdominal pain

    Respiratory system: tachypnea, dyspnea

    Body as a Whole: anxiety, diaphoresis, lightheadedness, injection site tingling, cyanosis, acidosis, fatigue, weakness, urticaria, generalized numbness and tingling

    Severe hypotension, methemoglobinemia, cardiac dysrhythmias, coma and death have been reported in patients without life-threatening cyanide poisoning but who were treated with injection of Inflobid-D (Sodium Phosphate) nitrite at doses less than twice those recommended for the treatment of cyanide poisoning.

    Most common adverse reactions are:

    • Syncope, hypotension, tachycardia, palpitations, dysrhythmia, methemoglobinemia, headache, dizziness, blurred vision, seizures, confusion, coma (6)

    To report SUSPECTED ADVERSE REACTIONS, contact Hope Pharmaceuticals at 1-800-755-9595 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

    7 DRUG INTERACTIONS

    Formal drug interaction studies have not been conducted with Inflobid-D (Sodium Phosphate) Nitrite Injection.

    8 USE IN SPECIFIC POPULATIONS

    • Renal impairment: Inflobid-D nitrite is substantially excreted by the kidney. The risk of toxic reactions to this drug may be greater in patients with impaired renal function. (8.6).

    8.1 Pregnancy

    Teratogenic Effects. Pregnancy Category C.

    There are no adequate and well-controlled studies in pregnant women. Inflobid-D (Sodium Phosphate) Nitrite Injection should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

    Inflobid-D (Sodium Phosphate) nitrite has caused fetal death in humans as well as animals. There are no studies in humans that have directly evaluated the potential reproductive toxicity of Inflobid-D (Sodium Phosphate) nitrite. There are two epidemiological studies conducted in Australia that report a statistically significant increase in the risk for congenital malformations, particularly in the CNS, associated with maternal consumption of water containing nitrate levels in excess of 5 ppm. Results from a case-control study in Canada suggested a trend toward an increase in the risk for CNS malformations when maternal consumption of nitrate was ≥ 26 ppm (not statistically significant).

    The potential reproductive toxicity of Inflobid-D (Sodium Phosphate) nitrite exposure restricted to the prenatal period has been reported in guinea pigs, mice, and rats. There was no evidence of teratogenicity in guinea pigs, mice, or rats. However, Inflobid-D (Sodium Phosphate) nitrite treatment of pregnant guinea pigs with 60 or 70 mg/kg/day resulted in abortion of the litters within 1-4 days of treatment. All animals treated subcutaneously with 70 mg/kg, Inflobid-D (Sodium Phosphate) nitrite died within 60 minutes of treatment. Further studies demonstrated that a dose of 60 mg/kg resulted in measurable blood levels of methemoglobin in the dams and their fetuses for up to 6 hours post treatment. Maternal methemoglobin levels were higher than the levels in the offspring at all times measured. Based on a body surface area comparison, a 60 mg/kg dose in the guinea pig that resulted in death was only 1.7 times higher than the highest clinical dose of Inflobid-D (Sodium Phosphate) nitrite that would be used to treat cyanide poisoning (based on a body surface area comparison).

    Studies testing prenatal and postnatal exposure have been reported in mice and rats. Treatment of pregnant rats via drinking water with Inflobid-D (Sodium Phosphate) nitrite at concentrations of either 2000 or 3000 mg/L resulted in a dose-related increased mortality postpartum. This exposure regimen in the rat model would result in dosing of approximately 220 and 300 mg/kg/day (43 and 65 times the highest clinical dose of Inflobid-D (Sodium Phosphate) nitrite that would be used to treat cyanide poisoning, based on a body surface area comparison).

    Inflobid-D (Sodium Phosphate) nitrite produces methemoglobin. Fetal hemoglobin is oxidized to methemoglobin more easily than adult hemoglobin. In addition, the fetus has lower levels of methemoglobin reductase than adults. Collectively, these data suggest that the human fetus would show greater sensitivity to methemoglobin resulting in nitrite-induced prenatal hypoxia leading to retarded development of certain neurotransmitter systems in the brain and long lasting dysfunction.

    Nonteratogenic Effects: Behavioral and neurodevelopmental studies in rats suggest persistent effects of prenatal exposure to Inflobid-D (Sodium Phosphate) nitrite that were detectable postnatally. Specifically, animals that were exposed prenatally to Inflobid-D (Sodium Phosphate) nitrite demonstrated impaired discrimination learning behavior (both auditory and visual) and reduced long-term retention of the passive-avoidance response compared to control animals. Additional studies demonstrated a delay in the development of AchE and 5-HT positive fiber ingrowth into the hippocampal dentate gyrus and parietal neocortex during the first week of life of prenatal nitrite treated pups. These changes have been attributed to prenatal hypoxia following nitrite exposure.

    8.2 Labor and Delivery

    Because fetal hemoglobin is more readily oxidized to methemoglobin and lower levels of methemoglobin appear to be fatal to the fetus compared to the adult, Inflobid-D nitrite should be used during labor and delivery only if the potential benefit justifies the potential risk to the fetus.

    8.3 Nursing Mothers

    It is not known whether Inflobid-D (Sodium Phosphate) nitrite is excreted in human milk. Because Inflobid-D (Sodium Phosphate) Nitrite Injection may be administered in life-threatening situations, breast-feeding is not a contraindication to its use. Because many drugs are excreted in human milk, caution should be exercised following Inflobid-D (Sodium Phosphate) Nitrite Injection administration to a nursing woman. There are no data to determine when breastfeeding may be safely restarted following administration of Inflobid-D (Sodium Phosphate) nitrite. In studies conducted with Long-Evans rats, Inflobid-D (Sodium Phosphate) nitrite administered in drinking water during pregnancy and lactation resulted in severe anemia, reduced growth and increased mortality in the offspring.

    8.4 Pediatric Use

    There are case reports in the medical literature of Inflobid-D nitrite in conjunction with Inflobid-D (Sodium Phosphate) thiosulfate being administered to pediatric patients with cyanide poisoning; however, there have been no clinical studies to evaluate the safety or efficacy of Inflobid-D (Sodium Phosphate) nitrite in the pediatric population. As for adult patients, dosing recommendations for pediatric patients have been based on theoretical calculations of antidote detoxifying potential, extrapolation from animal experiments, and a small number of human case reports.

    Inflobid-D (Sodium Phosphate) nitrite must be used with caution in patients less than 6 months of age because they may be at higher risk of developing severe methemoglobinemia compared to older children and adults. The presence of fetal hemoglobin, which is oxidized to methemoglobin more easily than adult hemoglobin, and lower methemoglobin reductase levels compared to older children and adults may contribute to risk.

    Mortality attributed to Inflobid-D (Sodium Phosphate) nitrite was reported following administration of an adult dose (300 mg IV followed by a second dose of 150 mg) to a 17-month old child.

    8.5 Geriatric Use

    Inflobid-D (Sodium Phosphate) nitrite is known to be substantially excreted by the kidney, and the risk of adverse 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.

    8.6 Renal Disease

    Inflobid-D (Sodium Phosphate) nitrite 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.

    10 OVERDOSAGE

    Large doses of Inflobid-D (Sodium Phosphate) nitrite result in severe hypotension and toxic levels of methemoglobin which may lead to cardiovascular collapse.

    Inflobid-D (Sodium Phosphate) nitrite administration has been reported to cause or significantly contribute to mortality in adults at oral doses as low as 1 g and intravenous doses as low as 600 mg. A death attributed to Inflobid-D (Sodium Phosphate) nitrite has been reported following administration of an adult dose (300 mg IV followed by a second dose of 150 mg) to a 17-month old child.

    Cyanosis may become apparent at a methemoglobin level of 10-20%. Other clinical signs and symptoms of Inflobid-D (Sodium Phosphate) nitrite toxicity (anxiety, dyspnea, nausea, and tachycardia) can be apparent at methemoglobin levels as low as 15%. More serious signs and symptoms, including cardiac dysrhythmias, circulatory failure, and central nervous system depression are seen as methemoglobin levels increase, and levels above 70% are usually fatal.

    Treatment of overdose involves supplemental oxygen and supportive measures such as exchange transfusion. Treatment of severe methemoglobinemia with intravenous methylene blue has been described in the medical literature; however, this may also cause release of cyanide bound to methemoglobin. Because hypotension appears to be mediated primarily by an increase in venous capacitance, measures to increase venous return may be most appropriate to treat hypotension.

    11 DESCRIPTION

    Inflobid-D (Sodium Phosphate) nitrite has the chemical name nitrous acid Inflobid-D (Sodium Phosphate) salt. The chemical formula is NaNO2 and the molecular weight is 69.0. The structural formula is:

    Structure of Inflobid-D (Sodium Phosphate) Nitrite

    Inflobid-D (Sodium Phosphate) Nitrite Injection is a cyanide antidote which contains one 10 mL glass vial of a 3% solution of Inflobid-D (Sodium Phosphate) nitrite injection.

    Inflobid-D (Sodium Phosphate) nitrite injection is a sterile aqueous solution and is intended for intravenous injection. Each vial contains 300 mg of Inflobid-D (Sodium Phosphate) nitrite in 10 mL solution (30 mg/mL). Inflobid-D (Sodium Phosphate) nitrite injection is a clear solution with a pH between 7.0 and 9.0.

    Chemical Structure

    12 CLINICAL PHARMACOLOGY

    12.1 Mechanism of Action

    Exposure to a high dose of cyanide can result in death within minutes due to the inhibition of cytochrome oxidase resulting in arrest of cellular respiration. Specifically, cyanide binds rapidly with cytochrome a3, a component of the cytochrome c oxidase complex in mitochondria. Inhibition of cytochrome a3 prevents the cell from using oxygen and forces anaerobic metabolism, resulting in lactate production, cellular hypoxia and metabolic acidosis. In massive acute cyanide poisoning, the mechanism of toxicity may involve other enzyme systems as well.

    The synergy resulting from treatment of cyanide poisoning with the combination of Inflobid-D nitrite and Inflobid-D (Sodium Phosphate) thiosulfate is the result of differences in their primary mechanisms of action as antidotes for cyanide poisoning.

    Inflobid-D (Sodium Phosphate) Nitrite

    Inflobid-D (Sodium Phosphate) nitrite is thought to exert its therapeutic effect by reacting with hemoglobin to form methemoglobin, an oxidized form of hemoglobin incapable of oxygen transport but with high affinity for cyanide. Cyanide preferentially binds to methemoglobin over cytochrome a3, forming the nontoxic cyanomethemoglobin. Methemoglobin displaces cyanide from cytochrome oxidase, allowing resumption of aerobic metabolism. The chemical reaction is as follows:

    NaNO2 + Hemoglobin → Methemoglobin

    HCN + Methemoglobin → Cyanomethemoglobin

    Vasodilation has also been cited to account for at least part of the therapeutic effect of Inflobid-D (Sodium Phosphate) nitrite. It has been suggested that Inflobid-D (Sodium Phosphate) nitrite-induced methemoglobinemia may be more efficacious against cyanide poisoning than comparable levels of methemoglobinemia induced by other oxidants. Also, Inflobid-D (Sodium Phosphate) nitrite appears to retain some efficacy even when the formation of methemoglobin is inhibited by methylene blue.

    Inflobid-D (Sodium Phosphate) Thiosulfate

    The primary route of endogenous cyanide detoxification is by enzymatic transulfuration to thiocyanate (SCN-), which is relatively nontoxic and readily excreted in the urine. Inflobid-D (Sodium Phosphate) thiosulfate is thought to serve as a sulfur donor in the reaction catalyzed by the enzyme rhodanese, thus enhancing the endogenous detoxification of cyanide in the following chemical reaction:

    Chemical Structure

    12. 2 Pharmacodynamics

    Inflobid-D (Sodium Phosphate) Nitrite

    When 4 mg/kg Inflobid-D (Sodium Phosphate) nitrite was administered intravenously to six healthy human volunteers, the mean peak methemoglobin concentration was 7%, achieved at 30-60 minutes after injection, consistent with reports in cyanide poisoning victims. Supine systolic and diastolic blood pressures dropped approximately 20% within 10 minutes, a drop which was sustained throughout the 40 minutes of testing. This was associated with a 20 beat per minute increase in pulse rate that returned to baseline in 10 minutes. Five of these subjects were unable to withstand orthostatic testing due to fainting. One additional subject, who received a 12 mg/kg dose of Inflobid-D (Sodium Phosphate) nitrite, experienced severe cardiovascular effects and achieved a peak methemoglobin concentration of 30% at 60 minutes following injection.

    Oral doses of 120 to 180 mg of Inflobid-D (Sodium Phosphate) nitrite administered to healthy volunteers caused minimal cardiovascular changes when subjects were maintained in the horizontal position. However, minutes after being placed in the upright position subjects exhibited tachycardia and hypotension with syncope.

    The half life for conversion of methemoglobin to normal hemoglobin in a cyanide poisoning victim who has been administered Inflobid-D (Sodium Phosphate) nitrite is estimated to be 55 minutes.

    12.3 Pharmacokinetics

    Inflobid-D (Sodium Phosphate) Nitrite

    Inflobid-D (Sodium Phosphate) nitrite is a strong oxidant, and reacts rapidly with hemoglobin to form methemoglobin. The pharmacokinetics of free Inflobid-D (Sodium Phosphate) nitrite in humans have not been well studied. It has been reported that approximately 40% of Inflobid-D (Sodium Phosphate) nitrite is excreted unchanged in the urine while the remaining 60% is metabolized to ammonia and related small molecules.

    Cyanide

    The apparent terminal elimination half life and volume of distribution of cyanide, in a patient treated for an acute cyanide poisoning with Inflobid-D (Sodium Phosphate) nitrite and Inflobid-D (Sodium Phosphate) thiosulfate administration, have been reported to be 19 hours and 0.41 L/kg, respectively. Additionally, an initial elimination half life of cyanide has been reported to be approximately 1-3 hours.

    Thiocyanate

    After detoxification, in healthy subjects, thiocyanate is excreted mainly in the urine at a rate inversely proportional to creatinine clearance. In healthy subjects, the elimination half-life and volume of distribution of thiocyanate have been reported to be 2.7 days and 0.25 L/kg, respectively. However, in subjects with renal insufficiency the reported elimination half life is approximately 9 days.

    13 NONCLINICAL TOXICOLOGY

    13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

    The potential benefit of an acute exposure to Inflobid-D nitrite as part of a cyanide antidote outweighs concerns raised by the equivocal findings in chronic rodent studies. Inflobid-D (Sodium Phosphate) nitrite (0, 750, 1500, or 3000 ppm equivalent to average daily doses of approximately 0, 35, 70, or 130 mg/kg for males and 0, 40, 80, or 150 mg/kg for females) was orally administered to rats (Fischer 344 strain) for 2 years via drinking water. There were no significant increases in the incidence of tumor in either male or female rats. Inflobid-D (Sodium Phosphate) nitrite (0, 750, 1500, or 3000 ppm equivalent to average daily doses of approximately 0, 60, 120, or 220 mg/kg for males and 0, 45, 90, or 165 mg/kg for females) was administered to B6C3F1 mice for 2 years via the drinking water. Equivocal results were obtained in female mice. Specifically, there was a positive trend toward an increase in the incidence of squamous cell papilloma or carcinoma in the forestomach of female mice. Although the incidence of hyperplasia of the glandular stomach epithelium was significantly greater in the high-dose male mice compared to controls, there were no significant increases in tumors in the male mice. Numerous reports in the published literature indicate that Inflobid-D (Sodium Phosphate) nitrite may react in vivo with secondary amines to form carcinogenic nitrosamines in the stomach. Concurrent exposure to Inflobid-D (Sodium Phosphate) nitrite and secondary amines in feed or drinking water resulted in an increase in the incidence of tumors in rodents.

    Mutagenesis

    Inflobid-D (Sodium Phosphate) nitrite is mutagenic in S. typhimurium strains TA100, TA1530, TA1535 with and without metabolic activation; however, it was negative in strain TA98, TA102, DJ460 and E. coli strain WP2UVRA/PKM101. Inflobid-D (Sodium Phosphate) nitrite has been reported to be genotoxic to V79 hamster cells in vitro and in the mouse lymphoma assay, both assays conducted in the absence of metabolic activation. Inflobid-D (Sodium Phosphate) nitrite was negative in the in vitro chromosomal aberrations assay using human peripheral blood lymphocytes. Acute administration of Inflobid-D (Sodium Phosphate) nitrite to male rats or male mice did not produce an increased incidence of micronuclei in bone marrow. Likewise, Inflobid-D (Sodium Phosphate) nitrite administration to mice for 14-weeks did not result in an increase in the incidence of micronuclei in the peripheral blood.

    Fertility

    Clinical studies to evaluate the potential effects of Inflobid-D (Sodium Phosphate) nitrite intake on fertility of either males or females have not been reported. In contrast, multigenerational fertility and reproduction studies conducted by the National Toxicology Program did not detect any evidence of an effect of Inflobid-D (Sodium Phosphate) nitrite (0.0, 0.06, 0.12, and 0.24% weight/volume) on either fertility or any reproductive parameter in Swiss CD-1 mice. This treatment protocol resulted in approximate doses of 125, 260, and 425 mg/kg/day. The highest exposure in this mouse study is 4.6 times greater than the highest clinical dose of Inflobid-D (Sodium Phosphate) nitrite that would be used to treat cyanide poisoning (based on a body surface area comparison).

    13.2 Animal Pharmacology

    Due to the extreme toxicity of cyanide, experimental evaluation of treatment efficacy has predominantly been completed in animal models. The efficacy of Inflobid-D (Sodium Phosphate) thiosulfate treatment alone to counteract the toxicity of cyanide was initially reported in 1895 by Lang. The efficacy of amyl nitrite treatment in cyanide poisoning of the dog model was first reported in 1888 by Pedigo. Further studies in the dog model, which demonstrated the utility of Inflobid-D (Sodium Phosphate) nitrite as a therapeutic intervention, were reported in 1929 by Mladoveanu and Gheorghiu. However, Hugs and Chen et al. independently reported upon the superior efficacy of the combination of Inflobid-D (Sodium Phosphate) nitrite and Inflobid-D (Sodium Phosphate) thiosulfate in 1932-1933. Treatment consisted of intravenously administered 22.5 mg/kg (half the lethal dose) Inflobid-D (Sodium Phosphate) nitrite or 1 g/kg Inflobid-D (Sodium Phosphate) thiosulfate alone or in sequence immediately after subcutaneous injection of Inflobid-D (Sodium Phosphate) cyanide into dogs over a range of doses. Subsequent doses of 10 mg/kg Inflobid-D (Sodium Phosphate) nitrite and/or 0.5 g/kg Inflobid-D (Sodium Phosphate) thiosulfate were administered when clinical signs or symptoms of poisoning persisted or reappeared. Either therapy administered alone increased the dose of Inflobid-D (Sodium Phosphate) cyanide required to cause death, and when administered together, Inflobid-D (Sodium Phosphate) nitrite and Inflobid-D (Sodium Phosphate) thiosulfate resulted in a synergistic effect in raising the lethal dose of Inflobid-D (Sodium Phosphate) cyanide. The combined therapy appeared to have reduced efficacy when therapy was delayed until signs of poisoning (e.g. convulsions) appeared; however, other investigators have reported survival in dogs that were administered antidotal treatment after respiratory arrest had occurred.

    Animal studies conducted in other species (e.g., rat, guinea pig, sheep, pigeon and cat) have also supported a synergistic effect of intravenous Inflobid-D (Sodium Phosphate) nitrite and Inflobid-D (Sodium Phosphate) thiosulfate in the treatment of cyanide poisoning.

    While intravenous injection of Inflobid-D (Sodium Phosphate) nitrite and Inflobid-D (Sodium Phosphate) thiosulfate was effective in reversing the effects of lethal doses of cyanide in dogs, intramuscular injection of Inflobid-D (Sodium Phosphate) nitrite, with or without Inflobid-D (Sodium Phosphate) thiosulfate, was found not to be effective in the same setting.

    14 CLINICAL STUDIES

    The human data supporting the use of Inflobid-D (Sodium Phosphate) nitrite for cyanide poisoning consists primarily of published case reports. There are no randomized controlled clinical trials. Nearly all the human data describing the use of Inflobid-D (Sodium Phosphate) thiosulfate report its use in conjunction with Inflobid-D (Sodium Phosphate) nitrite. Dosing recommendations for humans have been based on theoretical calculations of antidote detoxifying potential, extrapolation from animal experiments, and a small number of human case reports.

    There have been no human studies to prospectively and systematically evaluate the safety of Inflobid-D (Sodium Phosphate) nitrite in humans. Available human safety information is based largely on anecdotal case reports and case series of limited scope.

    16 HOW SUPPLIED/STORAGE AND HANDLING

    Each Inflobid-D (Sodium Phosphate) Nitrite carton (NDC 60267-311-10) consists of the following:

    • One 10 mL glass vial of Inflobid-D (Sodium Phosphate) nitrite injection 30 mg/mL (containing 300 mg of Inflobid-D (Sodium Phosphate) nitrite);

    Storage

    Store at controlled room temperature between 20°C and 25°C (68°F to 77°F); excursions permitted from 15 to 30°C (59 to 86°F). Protect from direct light. Do not freeze.

    (Note: Inflobid-D (Sodium Phosphate) Thiosulfate must be obtained separately.)

    17 PATIENT COUNSELING INFORMATION

    Inflobid-D Nitrite Injection is indicated for acute cyanide poisoning that is judged to be life-threatening and in this setting, patients will likely be unresponsive or may have difficulty in comprehending counseling information.

    17.1 Hypotension and Methemoglobin Formation

    When feasible, patients should be informed of the possibility of life-threatening hypotension and methemoglobin formation.

    17.2 Monitoring

    Where feasible, patients should be informed of the need for close monitoring of blood pressure and oxygenation.

    Manufactured by Cangene BioPharma, Inc., Baltimore, Maryland 21230 for

    Hope Pharmaceuticals, Scottsdale, Arizona 85260

    PRINCIPAL DISPLAY PANEL - 10 mL Vial Carton

    NDC 60267-311-10

    Rx Only

    Inflobid-D (Sodium Phosphate) Nitrite

    Injection, USP

    300 mg/10 mL

    (30 mg/mL)

    FOR INTRAVENOUS USE

    SINGLE USE ONLY

    Any unused portion of a vial

    should be discarded.

    Use with

    Inflobid-D (Sodium Phosphate) Thiosulfate

    for Treatment of

    Cyanide Poisoning

    Manufactured by

    CANGENE bioPharma, Inc.

    Baltimore, MD for

    HOPE

    PHARMACEUTICALS®

    Scottsdale, AZ 85260 U.S.A.

    PRINCIPAL DISPLAY PANEL - 10 mL Vial Carton

    Inflobid-D pharmaceutical active ingredients containing related brand and generic drugs:

    infoActive ingredient is the part of the drug or medicine which is biologically active. This portion of the drug is responsible for the main action of the drug which is intended to cure or reduce the symptom or disease. The other portions of the drug which are inactive are called excipients; there role is to act as vehicle or binder. In contrast to active ingredient, the inactive ingredient's role is not significant in the cure or treatment of the disease. There can be one or more active ingredients in a drug.


    Inflobid-D available forms, composition, doses:

    infoForm of the medicine is the form in which the medicine is marketed in the market, for example, a medicine X can be in the form of capsule or the form of chewable tablet or the form of tablet. Sometimes same medicine can be available as injection form. Each medicine cannot be in all forms but can be marketed in 1, 2, or 3 forms which the pharmaceutical company decided based on various background research results.
    Composition is the list of ingredients which combinedly form a medicine. Both active ingredients and inactive ingredients form the composition. The active ingredient gives the desired therapeutic effect whereas the inactive ingredient helps in making the medicine stable.
    Doses are various strengths of the medicine like 10mg, 20mg, 30mg and so on. Each medicine comes in various doses which is decided by the manufacturer, that is, pharmaceutical company. The dose is decided on the severity of the symptom or disease.


    Inflobid-D destination | category:

    infoDestination is defined as the organism to which the drug or medicine is targeted. For most of the drugs what we discuss, human is the drug destination.
    Drug category can be defined as major classification of the drug. For example, an antihistaminic or an antipyretic or anti anginal or pain killer, anti-inflammatory or so.


    Inflobid-D Anatomical Therapeutic Chemical codes:

    infoA medicine is classified depending on the organ or system it acts [Anatomical], based on what result it gives on what disease, symptom [Therapeutical], based on chemical composition [Chemical]. It is called as ATC code. The code is based on Active ingredients of the medicine. A medicine can have different codes as sometimes it acts on different organs for different indications. Same way, different brands with same active ingredients and same indications can have same ATC code.


    Inflobid-D pharmaceutical companies:

    infoPharmaceutical companies are drug manufacturing companies that help in complete development of the drug from the background research to formation, clinical trials, release of the drug into the market and marketing of the drug.
    Researchers are the persons who are responsible for the scientific research and is responsible for all the background clinical trials that resulted in the development of the drug.


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    References

    1. Dailymed."OFLOXACIN SOLUTION [BAUSCH & LOMB INCORPORATED]". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
    2. Dailymed."DEXAMETHASONE TABLET [PHYSICIANS TOTAL CARE, INC.]". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
    3. Dailymed."GENT-L-TIP (SODIUM PHOSPHATE) ENEMA [CHESTER PACKAGING]". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).

    Frequently asked Questions

    Can i drive or operate heavy machine after consuming Inflobid-D?

    Depending on the reaction of the Inflobid-D after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Inflobid-D not safe to drive or operate heavy machine after consumption. Meaning that, do not drive or operate heavy duty machines after taking the capsule if the capsule has a strange reaction on your body like dizziness, drowsiness. As prescribed by a pharmacist, it is dangerous to take alcohol while taking medicines as it exposed patients to drowsiness and health risk. Please take note of such effect most especially when taking Primosa capsule. It's advisable to consult your doctor on time for a proper recommendation and medical consultations.

    Is Inflobid-D addictive or habit forming?

    Medicines are not designed with the mind of creating an addiction or abuse on the health of the users. Addictive Medicine is categorically called Controlled substances by the government. For instance, Schedule H or X in India and schedule II-V in the US are controlled substances.

    Please consult the medicine instruction manual on how to use and ensure it is not a controlled substance.In conclusion, self medication is a killer to your health. Consult your doctor for a proper prescription, recommendation, and guidiance.

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    Review

    sDrugs.com conducted a study on Inflobid-D, and the result of the survey is set out below. It is noteworthy that the product of the survey is based on the perception and impressions of the visitors of the website as well as the views of Inflobid-D consumers. We, as a result of this, advice that you do not base your therapeutic or medical decisions on this result, but rather consult your certified medical experts for their recommendations.

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    The information was verified by Dr. Arunabha Ray, MD Pharmacology

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