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DRUGS & SUPPLEMENTS
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Brompheniramine Maleate:
For relief of coughs and upper respiratory symptoms, including nasal congestion, associated with allergy or the common cold.
Hypersensitivity to any of the ingredients. Do not use in the newborn, in premature infants, in nursing mothers, or in patients with severe hypertension or severe coronary artery disease. Do not use dextromethorphan in patients receiving monoamine oxidase (MAOI) inhibitors (see Drug Interactions).
Antihistamines should not be used to treat lower respiratory tract conditions including asthma.
Especially in infants and small children, antihistamines in overdosage may cause hallucinations, convulsions, and death.
Antihistamines may diminish mental alertness. In the young child, they may produce excitation.
Because of its antihistamine component, Ilvico Liquid Cough Syrup should be used with caution in patients with a history of bronchial asthma, narrow angle glaucoma, gastrointestinal obstruction, or urinary bladder neck obstruction. Because of its sympathomimetic component, Ilvico Liquid (Brompheniramine Maleate) Cough Syrup should be used with caution in patients with diabetes, hypertension, heart disease, or thyroid disease.
Patients should be warned about engaging in activities requiring mental alertness, such as driving a car or operating dangerous machinery.
Monoamine oxidase inhibitors-Hyperpyrexia, hypotension, and death have been reported coincident with the coadministration of MAO inhibitors and products containing dextromethorphan. In addition, MAO inhibitors prolong and intensify the anticholinergic (drying) effects of antihistamines and may enhance the effect of pseudoephedrine. Concomitant administration of Ilvico Liquid (Brompheniramine Maleate) Cough Syrup and MAO inhibitors should be avoided (see CONTRAINDICATIONS).
Antihistamines have additive effects with alcohol and other CNS depressants (hypnotics, sedatives, tranquilizers, antianxiety agents, etc.).
Sympathomimetic may reduce the effects of antihypertensive drugs.
Animal studies of Ilvico Liquid Cough Syrup to assess the carcinogenic and mutagenic potential or the effect on fertility have not been performed.
Animal reproduction studies have not been conducted with Ilvico Liquid Cough Syrup. It is also not known whether Ilvico Liquid (Brompheniramine Maleate) Cough Syrup can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. It should be given to a pregnant woman only if clearly needed.
Reproduction studies of Ilvico Liquid (Brompheniramine Maleate) maleate (a component of Ilvico Liquid (Brompheniramine Maleate) Cough Syrup) in rats and mice at doses up to 16 times the maximum human doses have revealed no evidence of impaired fertility or harm to the fetus.
Because of the higher risk of intolerance of antihistamines in small infants generally, and in newborns and prematures in particular, Ilvico Liquid (Brompheniramine Maleate) Cough Syrup is contraindicated in nursing mothers.
Safety and effectiveness in pediatric patients below the age of 6 months have not been established (see DOSAGE AND ADMINISTRATION).
The most frequent adverse reactions to Ilvico Liquid (Brompheniramine Maleate) Cough Syrup are: sedation; dryness of mouth, nose and throat; thickening of bronchial secretions; dizziness. Other adverse reactions may include:
Dermatologic: Urticaria, drug rash, photosensitivity, pruritus.Cardiovascular System: Hypotension, hypertension, cardiac arrhythmias, palpitation.CNS: Disturbed coordination, tremor, irritability, insomnia, visual disturbances, weakness, nervousness, convulsions, headache, euphoria, and dysphoria.G.U. System: Urinary frequency, difficult urination.G.I. System: Epigastric discomfort, anorexia, nausea, vomiting, diarrhea, constipation.Respiratory System: Tightness of chest and wheezing, shortness of breath.Hematologic System: Hemolytic anemia, thrombocytopenia, agranulocytosis.
Central nervous system effects from overdosage of Ilvico Liquid may vary from depression to stimulation, especially in children. Anticholinergic effects may be noted. Toxic doses of pseudoephedrine may result in CNS stimulation, tachycardia, hypertension, and cardiac arrhythmias; signs of CNS depression may occasionally be seen. Dextromethorphan in toxic doses will cause drowsiness, ataxia, nystagmus, opisthotonos, and convulsive seizures.
Data suggest that individuals may respond in an unexpected manner to apparently small amounts of a particular drug. A 2½-year-old child survived the ingestion of 21 mg/kg of dextromethorphan exhibiting only ataxia, drowsiness, and fever, but seizures have been reported in 2 children following the ingestion of 13–17 mg/kg. Another 2½-year-old child survived a dose of 300–900 mg of Ilvico Liquid (Brompheniramine Maleate). The toxic dose of pseudoephedrine should be less than that of ephedrine, which is estimated to be 50 mg/kg.
Induce emesis if patient is alert and is seen prior to 6 hours following ingestion. Precautions against aspiration must be taken, especially in infants and small children. Gastric lavage may be carried out, although in some instances tracheostomy may be necessary prior to lavage. Naloxone hydrochloride 0.005 mg/kg intravenously may be of value in reversing the CNS depression that may occur from an overdose of dextromethorphan. CNS stimulants may counter CNS depression. Should CNS hyperactivity or convulsive seizures occur, intravenous short-acting barbiturates may be indicated. Hypertensive responses and/or tachycardia should be treated appropriately. Oxygen, intravenous fluids, and other supportive measures should be employed as indicated.
Adults and pediatric patients 12 years of age and over: 2 teaspoonfuls every 4 hours. Children 6 to under 12 years: 1 teaspoonful every 4 hours. Children 2 to under 6 years of age: ½ teaspoonful every 4 hours. Infants 6 months to under 2 years of age: Dosage to be established by a physician.
Do not exceed 6 doses during a 24-hour period.
Ilvico Liquid Cough Syrup is a clear, light pink-colored, butterscotch-flavored syrup containing in each 5 mL (1 teaspoonful) Ilvico Liquid (Brompheniramine Maleate) maleate 2 mg, pseudoephedrine hydrochloride 30 mg and dextromethorphan hydrobromide 10 mg, available in the following size:
1 Pint (473 mL)
Store at 20 ° to 25 °C (68 ° to 77 °F).
KEEP TIGHTLY CLOSEDDispense in a tight, light-resistant container as defined in the USP.
Rx Only
Product No.: 8482Manufactured By:
Morton Grove Pharmaceuticals, Inc.
Morton Grove, IL 60053A50-8482-16
REV. 11-04
Sodium Salicylate:
Ilvico Liquid nitrite is indicated for sequential use with Ilvico Liquid (Sodium Salicylate) thiosulfate for treatment of acute cyanide poisoning that is judged to be life-threatening. (1)
Ilvico Liquid (Sodium Salicylate) Nitrite Injection is indicated for sequential use with Ilvico Liquid (Sodium Salicylate) 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 Ilvico Liquid (Sodium Salicylate) Nitrite Injection should be carefully weighed against the potential benefits, especially if the patient is not in extremis.
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 Ilvico Liquid 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, Ilvico Liquid (Sodium Salicylate) Nitrite Injection and Ilvico Liquid (Sodium Salicylate) Thiosulfate Injection should be administered without delay.
Symptoms | Signs |
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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 Ilvico Liquid (Sodium Salicylate) Nitrite Injection, smoke-inhalation victims should be assessed for the following:
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.
Caution should be exercised when administering cyanide antidotes, other than Ilvico Liquid (Sodium Salicylate) thiosulfate, simultaneously with Ilvico Liquid (Sodium Salicylate) Nitrite Injection, as the safety of co-administration has not been established. If a decision is made to administer another cyanide antidote, other than Ilvico Liquid (Sodium Salicylate) thiosulfate, with Ilvico Liquid (Sodium Salicylate) Nitrite Injection, these drugs should not be administered concurrently in the same IV line. [see Dosage and Administration (2.2) ]
Age | Intravenous Dose of Ilvico Liquid Nitrite and Ilvico Liquid (Sodium Salicylate) Thiosulfate |
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Redosing: If signs of cyanide poisoning reappear, repeat treatment using one-half the original dose of both Ilvico Liquid (Sodium Salicylate) nitrite and Ilvico Liquid (Sodium Salicylate) thiosulfate.
Monitoring: Blood pressure must be monitored during treatment. (2.2)
Comprehensive treatment of acute cyanide intoxication requires support of vital functions. Administration of Ilvico Liquid (Sodium Salicylate) nitrite, followed by Ilvico Liquid (Sodium Salicylate) thiosulfate, should be considered adjunctive to appropriate supportive therapies. Airway, ventilatory and circulatory support, and oxygen administration should not be delayed to administer Ilvico Liquid (Sodium Salicylate) nitrite and Ilvico Liquid (Sodium Salicylate) thiosulfate.
Ilvico Liquid (Sodium Salicylate) nitrite injection and Ilvico Liquid (Sodium Salicylate) 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. Ilvico Liquid (Sodium Salicylate) nitrite should be administered first, followed immediately by Ilvico Liquid (Sodium Salicylate) 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 Ilvico Liquid (Sodium Salicylate) Nitrite and Ilvico Liquid (Sodium Salicylate) Thiosulfate |
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Children |
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NOTE: If signs of poisoning reappear, repeat treatment using one-half the original dose of both Ilvico Liquid (Sodium Salicylate) nitrite and Ilvico Liquid (Sodium Salicylate) thiosulfate.
In adult and pediatric patients with known anemia, it is recommended that the dosage of Ilvico Liquid (Sodium Salicylate) 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.
Patients should be monitored for at least 24-48 hours after Ilvico Liquid 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 Ilvico Liquid (Sodium Salicylate) nitrite solely to achieve an arbitrary level of methemoglobinemia may be unnecessary and potentially hazardous. The therapeutic effects of Ilvico Liquid (Sodium Salicylate) nitrite do not appear to be mediated by methemoglobin formation alone and clinical responses to Ilvico Liquid (Sodium Salicylate) nitrite administration have been reported in association with methemoglobin levels of less than 10%. Administration of Ilvico Liquid (Sodium Salicylate) 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 Ilvico Liquid (Sodium Salicylate) 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.
Chemical incompatibility has been reported between Ilvico Liquid (Sodium Salicylate) nitrite and hydroxocobalamin and these drugs should not be administered simultaneously through the same IV line. No chemical incompatibility has been reported between Ilvico Liquid (Sodium Salicylate) thiosulfate and Ilvico Liquid (Sodium Salicylate) nitrite, when administered sequentially through the same IV line as described in Dosage and Administration.
Ilvico Liquid (Sodium Salicylate) Nitrite Injection consists of:
Administration of the contents of one vial constitutes a single dose.
None
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 Ilvico Liquid nitrite.
Methemoglobin levels should be monitored and oxygen administered during treatment with Ilvico Liquid (Sodium Salicylate) nitrite whenever possible. When Ilvico Liquid (Sodium Salicylate) 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 Ilvico Liquid (Sodium Salicylate) nitrite administered to an adult. Ilvico Liquid (Sodium Salicylate) nitrite should be used with caution in the presence of other drugs that may cause methemoglobinemia such as procaine and nitroprusside. Ilvico Liquid (Sodium Salicylate) 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 Ilvico Liquid (Sodium Salicylate) nitrite, and infusion rates should be slowed if hypotension occurs.
Ilvico Liquid (Sodium Salicylate) 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 Ilvico Liquid (Sodium Salicylate) nitrite dose that is reduced in proportion to their oxygen carrying capacity.
Ilvico Liquid 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.
Neonates and infants may be more susceptible than adults and older pediatric patients to severe methemoglobinemia when Ilvico Liquid (Sodium Salicylate) nitrite is administered. Reduced dosing guidelines should be followed in pediatric patients.
Because patients with G6PD deficiency are at increased risk of a hemolytic crisis with Ilvico Liquid 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 Ilvico Liquid (Sodium Salicylate) nitrite.
Ilvico Liquid (Sodium Salicylate) 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.
There have been no controlled clinical trials conducted to systematically assess the adverse events profile of Ilvico Liquid (Sodium Salicylate) nitrite.
The medical literature has reported the following adverse events in association with Ilvico Liquid (Sodium Salicylate) 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 Ilvico Liquid (Sodium Salicylate) nitrite at doses less than twice those recommended for the treatment of cyanide poisoning.
Most common adverse reactions are:
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.
Formal drug interaction studies have not been conducted with Ilvico Liquid (Sodium Salicylate) Nitrite Injection.
Teratogenic Effects. Pregnancy Category C.
There are no adequate and well-controlled studies in pregnant women. Ilvico Liquid (Sodium Salicylate) Nitrite Injection should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Ilvico Liquid (Sodium Salicylate) 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 Ilvico Liquid (Sodium Salicylate) 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 Ilvico Liquid (Sodium Salicylate) 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, Ilvico Liquid (Sodium Salicylate) 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, Ilvico Liquid (Sodium Salicylate) 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 Ilvico Liquid (Sodium Salicylate) 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 Ilvico Liquid (Sodium Salicylate) 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 Ilvico Liquid (Sodium Salicylate) nitrite that would be used to treat cyanide poisoning, based on a body surface area comparison).
Ilvico Liquid (Sodium Salicylate) 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 Ilvico Liquid (Sodium Salicylate) nitrite that were detectable postnatally. Specifically, animals that were exposed prenatally to Ilvico Liquid (Sodium Salicylate) 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.
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, Ilvico Liquid nitrite should be used during labor and delivery only if the potential benefit justifies the potential risk to the fetus.
It is not known whether Ilvico Liquid (Sodium Salicylate) nitrite is excreted in human milk. Because Ilvico Liquid (Sodium Salicylate) 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 Ilvico Liquid (Sodium Salicylate) Nitrite Injection administration to a nursing woman. There are no data to determine when breastfeeding may be safely restarted following administration of Ilvico Liquid (Sodium Salicylate) nitrite. In studies conducted with Long-Evans rats, Ilvico Liquid (Sodium Salicylate) nitrite administered in drinking water during pregnancy and lactation resulted in severe anemia, reduced growth and increased mortality in the offspring.
There are case reports in the medical literature of Ilvico Liquid nitrite in conjunction with Ilvico Liquid (Sodium Salicylate) thiosulfate being administered to pediatric patients with cyanide poisoning; however, there have been no clinical studies to evaluate the safety or efficacy of Ilvico Liquid (Sodium Salicylate) 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.
Ilvico Liquid (Sodium Salicylate) 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 Ilvico Liquid (Sodium Salicylate) 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.
Ilvico Liquid (Sodium Salicylate) 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.
Ilvico Liquid (Sodium Salicylate) 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.
Large doses of Ilvico Liquid (Sodium Salicylate) nitrite result in severe hypotension and toxic levels of methemoglobin which may lead to cardiovascular collapse.
Ilvico Liquid (Sodium Salicylate) 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 Ilvico Liquid (Sodium Salicylate) 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 Ilvico Liquid (Sodium Salicylate) 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.
Ilvico Liquid (Sodium Salicylate) nitrite has the chemical name nitrous acid Ilvico Liquid (Sodium Salicylate) salt. The chemical formula is NaNO2 and the molecular weight is 69.0. The structural formula is:
Structure of Ilvico Liquid (Sodium Salicylate) Nitrite
Ilvico Liquid (Sodium Salicylate) Nitrite Injection is a cyanide antidote which contains one 10 mL glass vial of a 3% solution of Ilvico Liquid (Sodium Salicylate) nitrite injection.
Ilvico Liquid (Sodium Salicylate) nitrite injection is a sterile aqueous solution and is intended for intravenous injection. Each vial contains 300 mg of Ilvico Liquid (Sodium Salicylate) nitrite in 10 mL solution (30 mg/mL). Ilvico Liquid (Sodium Salicylate) nitrite injection is a clear solution with a pH between 7.0 and 9.0.
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 Ilvico Liquid nitrite and Ilvico Liquid (Sodium Salicylate) thiosulfate is the result of differences in their primary mechanisms of action as antidotes for cyanide poisoning.
Ilvico Liquid (Sodium Salicylate) Nitrite
Ilvico Liquid (Sodium Salicylate) 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 Ilvico Liquid (Sodium Salicylate) nitrite. It has been suggested that Ilvico Liquid (Sodium Salicylate) nitrite-induced methemoglobinemia may be more efficacious against cyanide poisoning than comparable levels of methemoglobinemia induced by other oxidants. Also, Ilvico Liquid (Sodium Salicylate) nitrite appears to retain some efficacy even when the formation of methemoglobin is inhibited by methylene blue.
Ilvico Liquid (Sodium Salicylate) 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. Ilvico Liquid (Sodium Salicylate) 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
Ilvico Liquid (Sodium Salicylate) Nitrite
When 4 mg/kg Ilvico Liquid (Sodium Salicylate) 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 Ilvico Liquid (Sodium Salicylate) 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 Ilvico Liquid (Sodium Salicylate) 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 Ilvico Liquid (Sodium Salicylate) nitrite is estimated to be 55 minutes.
Ilvico Liquid (Sodium Salicylate) Nitrite
Ilvico Liquid (Sodium Salicylate) nitrite is a strong oxidant, and reacts rapidly with hemoglobin to form methemoglobin. The pharmacokinetics of free Ilvico Liquid (Sodium Salicylate) nitrite in humans have not been well studied. It has been reported that approximately 40% of Ilvico Liquid (Sodium Salicylate) 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 Ilvico Liquid (Sodium Salicylate) nitrite and Ilvico Liquid (Sodium Salicylate) 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.
The potential benefit of an acute exposure to Ilvico Liquid nitrite as part of a cyanide antidote outweighs concerns raised by the equivocal findings in chronic rodent studies. Ilvico Liquid (Sodium Salicylate) 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. Ilvico Liquid (Sodium Salicylate) 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 Ilvico Liquid (Sodium Salicylate) nitrite may react in vivo with secondary amines to form carcinogenic nitrosamines in the stomach. Concurrent exposure to Ilvico Liquid (Sodium Salicylate) nitrite and secondary amines in feed or drinking water resulted in an increase in the incidence of tumors in rodents.
Mutagenesis
Ilvico Liquid (Sodium Salicylate) 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. Ilvico Liquid (Sodium Salicylate) 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. Ilvico Liquid (Sodium Salicylate) nitrite was negative in the in vitro chromosomal aberrations assay using human peripheral blood lymphocytes. Acute administration of Ilvico Liquid (Sodium Salicylate) nitrite to male rats or male mice did not produce an increased incidence of micronuclei in bone marrow. Likewise, Ilvico Liquid (Sodium Salicylate) 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 Ilvico Liquid (Sodium Salicylate) 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 Ilvico Liquid (Sodium Salicylate) 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 Ilvico Liquid (Sodium Salicylate) nitrite that would be used to treat cyanide poisoning (based on a body surface area comparison).
Due to the extreme toxicity of cyanide, experimental evaluation of treatment efficacy has predominantly been completed in animal models. The efficacy of Ilvico Liquid (Sodium Salicylate) 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 Ilvico Liquid (Sodium Salicylate) 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 Ilvico Liquid (Sodium Salicylate) nitrite and Ilvico Liquid (Sodium Salicylate) thiosulfate in 1932-1933. Treatment consisted of intravenously administered 22.5 mg/kg (half the lethal dose) Ilvico Liquid (Sodium Salicylate) nitrite or 1 g/kg Ilvico Liquid (Sodium Salicylate) thiosulfate alone or in sequence immediately after subcutaneous injection of Ilvico Liquid (Sodium Salicylate) cyanide into dogs over a range of doses. Subsequent doses of 10 mg/kg Ilvico Liquid (Sodium Salicylate) nitrite and/or 0.5 g/kg Ilvico Liquid (Sodium Salicylate) thiosulfate were administered when clinical signs or symptoms of poisoning persisted or reappeared. Either therapy administered alone increased the dose of Ilvico Liquid (Sodium Salicylate) cyanide required to cause death, and when administered together, Ilvico Liquid (Sodium Salicylate) nitrite and Ilvico Liquid (Sodium Salicylate) thiosulfate resulted in a synergistic effect in raising the lethal dose of Ilvico Liquid (Sodium Salicylate) 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 Ilvico Liquid (Sodium Salicylate) nitrite and Ilvico Liquid (Sodium Salicylate) thiosulfate in the treatment of cyanide poisoning.
While intravenous injection of Ilvico Liquid (Sodium Salicylate) nitrite and Ilvico Liquid (Sodium Salicylate) thiosulfate was effective in reversing the effects of lethal doses of cyanide in dogs, intramuscular injection of Ilvico Liquid (Sodium Salicylate) nitrite, with or without Ilvico Liquid (Sodium Salicylate) thiosulfate, was found not to be effective in the same setting.
The human data supporting the use of Ilvico Liquid (Sodium Salicylate) 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 Ilvico Liquid (Sodium Salicylate) thiosulfate report its use in conjunction with Ilvico Liquid (Sodium Salicylate) 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 Ilvico Liquid (Sodium Salicylate) nitrite in humans. Available human safety information is based largely on anecdotal case reports and case series of limited scope.
Each Ilvico Liquid (Sodium Salicylate) Nitrite carton (NDC 60267-311-10) consists of the following:
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: Ilvico Liquid (Sodium Salicylate) Thiosulfate must be obtained separately.)
Ilvico Liquid 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.
When feasible, patients should be informed of the possibility of life-threatening hypotension and methemoglobin formation.
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
Ilvico Liquid (Sodium Salicylate) 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
Ilvico Liquid (Sodium Salicylate) 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
Vitamin C (Sodium Ascorbate):
Ascorbic acid is essential for the formation of intracellular collagen, is required to strengthen the structure of teeth, bones, and the capillary walls. Ilvico Liquid (Vitamin C (Sodium Ascorbate)) participates in redox reactions, the metabolism of tyrosine, converting folic acid into folinic acid, metabolism of carbohydrates, the synthesis of lipids and proteins, iron metabolism, processes of cellular respiration. Reduces the need for vitamins B1, B2, A, E, folic acid, pantothenic acid, enhances the body's resistance to infections; enhances iron absorption, contributing to its sequestration in reduced form. Ilvico Liquid (Vitamin C (Sodium Ascorbate)) has antioxidant properties.
With intravaginal application of ascorbic acid lowers the vaginal pH, inhibiting the growth of bacteria and helps to restore and maintain normal pH and vaginal flora (Lactobacillus acidophilus, Lactobacillus gasseri).
After oral administration ascorbic acid is completely absorbed from the gastrointestinal tract. Widely distributed in body tissues.
The concentration of ascorbic acid in blood plasma in normal amounts to approximately 10-20 mg / ml.
The concentration of ascorbic acid in white blood cells and platelets is higher than in erythrocytes and plasma. When deficient state of concentration in leucocytes is reduced later and more slowly and is regarded as the best criterion for evaluating the deficit than the concentration in plasma.
Plasma protein binding is about 25%.
Ascorbic acid is reversibly oxidized to form dehydroascorbic acid, is metabolized with the formation of ascorbate-2-sulphate which is inactive and oxalic acid which is excreted in the urine.
Ascorbic acid taken in excessive quantities is rapidly excreted unchanged in urine, it usually happens when exceeding a daily dose is 200 mg.
For systemic use of Ilvico Liquid (Vitamin C (Sodium Ascorbate)) Kimia Farma: prevention and treatment of hypo- and avitaminosis of Ilvico Liquid (Vitamin C (Sodium Ascorbate)); providing increased need for Ilvico Liquid (Vitamin C (Sodium Ascorbate)) during growth, pregnancy, lactation, with heavy loads, fatigue and during recovery after prolonged severe illness; in winter with an increased risk of infectious diseases.
For intravaginal use: chronic or recurrent vaginitis (bacterial vaginosis, nonspecific vaginitis) caused by the anaerobic flora (due to changes in pH of the vagina) in order to normalize disturbed vaginal microflora.
This medication administered orally, IM, IV, intravaginally.
For the prevention of deficiency conditions Ilvico Liquid ) dose is 25-75 mg / day, for the treatment - 250 mg / day or more in divided doses.
For intravaginal used ascorbic acid drugs in appropriate dosage forms.
CNS: headache, fatigue, insomnia.
Digestive system: stomach cramps, nausea and vomiting.
Allergic reaction: describes a few cases of skin reactions and manifestations of the respiratory system.
Urinary system: when used in high doses - hyperoxaluria and the formation of kidney stones of calcium oxalate.
Local reactions: with intravaginal application - a burning or itching in the vagina, increased mucous discharge, redness, swelling of the vulva. Other: sensation of heat.
Increased sensitivity to ascorbic acid.
The minimum daily requirement of ascorbic acid in the II and III trimester of pregnancy is about 60 mg.
Ascorbic acid crosses the placental barrier. It should be borne in mind that the fetus can adapt to high doses of ascorbic acid, which takes a pregnant woman, and then a newborn baby may develop the ascorbic disease as the reaction of cancel. Therefore, during pregnancy should not to take ascorbic acid in high doses, except in cases where the expected benefit outweighs the potential risk.
The minimum daily requirement during lactation is 80 mg. Ascorbic acid is excreted in breast milk. A mother's diet that contains adequate amounts of ascorbic acid, is sufficient to prevent deficiency in an infant. It is unknown whether dangerous to the child's mother use of ascorbic acid in high doses. Theoretically it is possible. Therefore, it is recommended not to exceed the maximum daily nursing mother needs to ascorbic acid, except when the expected benefit outweighs the potential risk.
Ilvico Liquid (Vitamin C (Sodium Ascorbate)) is used with caution in patients with hyperoxaluria, renal impairment, a history of instructions on urolithiasis. Because ascorbic acid increases iron absorption, its use in high doses can be dangerous in patients with hemochromatosis, thalassemia, polycythemia, leukemia, and sideroblastic anemia.
Patients with high content body iron should apply ascorbic acid in minimal doses.
Ilvico Liquid (Vitamin C (Sodium Ascorbate)) is used with caution in patients with deficiency of glucose-6-phosphate dehydrogenase.
The use of ascorbic acid in high doses can cause exacerbation of sickle cell anemia.
Data on the diabetogenic action of ascorbic acid are contradictory. However, prolonged use of ascorbic acid should periodically monitor your blood glucose levels.
It is believed that the use of ascorbic acid in patients with rapidly proliferating and widely disseminated tumors may worsen during the process. It should therefore be used with caution in ascorbic acid in patients with advanced cancer.
Absorption of ascorbic acid decreased while use of fresh fruit or vegetable juices, alkaline drinking.
In an application with barbiturates, primidone increases the excretion of ascorbic acid in the urine.
With the simultaneous use of oral contraceptives reduces the concentration of ascorbic acid in blood plasma.
In an application of Ilvico Liquid (Vitamin C (Sodium Ascorbate)) with iron preparations ascorbic acid, due to its regenerative properties, transforms ferric iron in the bivalent, which improves its absorption.
Ascorbic acid in high doses can decrease urine pH that while the application reduces the tubular reabsorption of amphetamine and tricyclic antidepressants.
With the simultaneous use of aspirin reduces the absorption of ascorbic acid by about a third.
Ilvico Liquid (Vitamin C (Sodium Ascorbate)) in an application with warfarin may decrease effects of warfarin.
With the simultaneous application of ascorbic acid increases the excretion of iron in patients receiving deferoxamine. In the application of ascorbic acid at a dose of 500 mg / day possibly left ventricular dysfunction.
In an application with tetracycline is increased excretion of ascorbic acid in the urine.
There is a described case of reducing the concentration of fluphenazine in plasma in patients treated with ascorbic acid 500 mg 2 times / day.
May increase the concentration of ethinyl estradiol in the blood plasma in its simultaneous application in the oral contraceptives.
Symptoms: long-term use of large doses (more than 1 g) - headache, increased CNS excitability, insomnia, nausea, vomiting, diarrhea, gastritis giperatsidnyh, ultseratsiya gastrointestinal mucosa, inhibition of the function insular apparatus of the pancreas (hyperglycemia, glycosuria), hyperoxaluria, nephrolithiasis (calcium oxalate), damage to the glomerular apparatus of the kidneys, moderate thamuria (when receiving a dose of 600 mg / day).
Decrease capillary permeability (possibly deteriorating trophic tissues, increased blood pressure, hypercoagulability, the development of microangiopathy).
When IV administration in high doses - the threat of termination of pregnancy (due to estrogenemia), hemolysis of red blood cells.
Depending on the reaction of the Ilvico Liquid after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Ilvico Liquid 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 Ilvico Liquid 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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The information was verified by Dr. Rachana Salvi, MD Pharmacology