DRUGS & SUPPLEMENTS
Oligostim Soufre uses
1 INDICATIONS AND USAGE
Oligostim Soufre is indicated for sequential use with sodium nitrite for treatment of acute cyanide poisoning that is judged to be life-threatening.
Oligostim Soufre Injection is indicated for sequential use with sodium nitrite for the treatment of acute cyanide poisoning that is judged to be life-threatening. When the diagnosis of cyanide poisoning is uncertain, the potential risks associated with Oligostim Soufre 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 sodium 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, Oligostim Soufre Injection and Sodium Nitrite Injection should be administered without delay.
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.
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 Oligostim Soufre 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.
1.3 Use with Other Cyanide Antidotes
Caution should be exercised when administering cyanide antidotes, other than sodium nitrite, simultaneously with Oligostim Soufre Injection, as the safety of co-administration has not been established. If a decision is made to administer another cyanide antidote, other than sodium nitrite, with Oligostim Soufre Injection, these drugs should not be administered concurrently in the same IV line. [see Dosage and Administration (2.2) ]
2 DOSAGE AND ADMINISTRATION
Redosing: If signs of cyanide poisoning reappear, repeat treatment using one-half the original dose of both sodium nitrite and Oligostim Soufre.
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 sodium nitrite and Oligostim Soufre should be considered adjunctive to appropriate supportive therapies. Airway, ventilatory and circulatory support, and oxygen administration should not be delayed to administer sodium nitrite and Oligostim Soufre.
Sodium nitrite injection and Oligostim Soufre 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. Sodium nitrite should be administered first, followed immediately by Oligostim Soufre. Blood pressure must be monitored during infusion in both adults and children. The rate of infusion should be decreased if significant hypotension is noted.
NOTE: If signs of poisoning reappear, repeat treatment using one-half the original dose of both sodium nitrite and Oligostim Soufre.
In adult and pediatric patients with known anemia, it is recommended that the dosage of sodium 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 Oligostim Soufre 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.
2.3 Incompatibility Information
Chemical incompatibility has been reported between Oligostim Soufre Injection and hydroxocobalamin and these drugs should not be administered simultaneously through the same IV line. No chemical incompatibility has been reported between Oligostim Soufre and sodium nitrite, when administered sequentially through the same IV line as described in Dosage and Administration.
3 DOSAGE FORMS AND STRENGTHS
Oligostim Soufre Injection consists of:
Administration of the contents of one vial constitutes a single dose.
5 WARNINGS AND PRECAUTIONS
Oligostim Soufre drug product may contain trace impurities of sodium sulfite. The presence of a trace amount of sulfites in this product should not deter administration of the drug for treatment of emergency situations, even if the patient is sulfite-sensitive.
6 ADVERSE REACTIONS
There have been no controlled clinical trials conducted to systematically assess the adverse events profile of Oligostim Soufre.
The medical literature has reported the following adverse events in association with Oligostim Soufre 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: hypotension
Central nervous system: headache, disorientation
Gastrointestinal system: nausea, vomiting
Hematological: prolonged bleeding time
Body as a Whole: salty taste in mouth, warm sensation over body
In humans, rapid administration of concentrated solutions or solutions not freshly prepared, and administration of large doses of Oligostim Soufre have been associated with a higher incidence of nausea and vomiting. However, administration of 0.1 g Oligostim Soufre per pound up to a maximum of 15 g in a 10-15% solution over 10-15 minutes was associated with nausea and vomiting in 7 of 26 patients without concomitant cyanide intoxication.
In a series of 11 human subjects, a single intravenous infusion of 50 mL of 50% Oligostim Soufre was associated with increases in clotting time 1-3 days after administration. However, no significant changes were observed in other hematological parameters.
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.
7 DRUG INTERACTIONS
Formal drug interaction studies have not been conducted with Oligostim Soufre Injection.
8 USE IN SPECIFIC POPULATIONS
Teratogenic Effects. Pregnancy Category C.
There are no adequate and well-controlled studies in pregnant women. Oligostim Soufre Injection should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
There are no reported epidemiological studies of congenital anomalies in infants born to women treated with Oligostim Soufre during pregnancy. In animal studies, there are no teratogenic effects in offspring of hamsters treated during pregnancy with Oligostim Soufre in doses similar to those given intravenously to treat cyanide poisoning in humans. Other studies suggest that treatment with Oligostim Soufre ameliorates the teratogenic effects of maternal cyanide poisoning in hamsters. In other studies, Oligostim Soufre was not embryotoxic or teratogenic in mice, rats, hamsters, or rabbits at maternal doses of up to 550, 400, 400 and 580 mg/kg/day, respectively.
8.3 Nursing Mothers
It is not known whether Oligostim Soufre is excreted in human milk. Because Oligostim Soufre 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 Oligostim Soufre Injection administration to a nursing woman. There are no data to determine when breastfeeding may be safely restarted following administration of Oligostim Soufre.
8.4 Pediatric Use
There are case reports in the medical literature of sodium nitrite in conjunction with Oligostim Soufre being administered to pediatric patients with cyanide poisoning; however, there have been no clinical studies to evaluate the safety or efficacy of Oligostim Soufre 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.
8.5 Geriatric Use
Oligostim Soufre 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
Oligostim Soufre 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.
There is limited information about the effects of large doses of Oligostim Soufre in humans. Oral administration of 3 g Oligostim Soufre per day for 1-2 weeks in humans resulted in reductions in room air arterial oxygen saturation to as low as 75%, which was due to a rightward shift in the oxygen hemoglobin dissociation curve. The subjects returned to baseline oxygen saturations 1 week after discontinuation of Oligostim Soufre. A single intravenous administration of 20 mL of 10% Oligostim Soufre reportedly did not change oxygen saturations.
Oligostim Soufre has the chemical name thiosulfuric acid, disodium salt, pentahydrate. The chemical formula is Na2S2O3- 5H2O and the molecular weight is 248.17. The structural formula is:
Structure of Oligostim Soufre Pentahydrate
Oligostim Soufre Injection is a cyanide antidote which contains one 50 mL glass vial containing a 25% solution of Oligostim Soufre injection.
Oligostim Soufre injection is a sterile aqueous solution and is intended for intravenous injection. Each vial contains 12.5 grams of Oligostim Soufre in 50 mL solution (250 mg/mL). Each mL also contains 2.8 mg boric acid and 4.4 mg of potassium chloride. The pH of the solution is adjusted with boric acid and/or sodium hydroxide. Oligostim Soufre injection is a clear solution with a pH between 7.5 and 9.5.
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 sodium nitrite and Oligostim Soufre is the result of differences in their primary mechanisms of action as antidotes for cyanide poisoning.
Sodium 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 sodium nitrite. It has been suggested that sodium nitrite-induced methemoglobinemia may be more efficacious against cyanide poisoning than comparable levels of methemoglobinemia induced by other oxidants. Also, sodium nitrite appears to retain some efficacy even when the formation of methemoglobin is inhibited by methylene blue.
The primary route of endogenous cyanide detoxification is by enzymatic transulfuration to thiocyanate, which is relatively nontoxic and readily excreted in the urine. Oligostim Soufre 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:
12. 2 Pharmacodynamics
In dogs, pretreatment with Oligostim Soufre to achieve a steady state level of 2 µmol/mL increased the rate of conversion of cyanide to thiocyanate over 30-fold.
Thiosulfate taken orally is not systemically absorbed. Most of the thiosulfate is oxidized to sulfate or is incorporated into endogenous sulphur compounds; a small proportion is excreted through the kidneys. Approximately 20-50% of exogenously administered thiosulfate is eliminated unchanged via the kidneys. After an intravenous injection of 1 g Oligostim Soufre in patients, the reported serum thiosulfate half-life was approximately 20 minutes. However, after an intravenous injection of a substantially higher dose of Oligostim Soufre (150 mg/kg, that is, 9 g for 60 kg body weight) in normal healthy men, the reported elimination half-life was 182 minutes.
The apparent terminal elimination half life and volume of distribution of cyanide, in a patient treated for an acute cyanide poisoning with sodium nitrite and Oligostim Soufre 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.
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
Long-term studies in animals have not been performed to evaluate the potential carcinogenicity of Oligostim Soufre.
The mutagenic potential of Oligostim Soufre has been examined in the in vitro Bacterial Reverse Mutation Assay. Oligostim Soufre was not mutagenic in the absence of metabolic activation in S. typhimurium strains TA98, TA100, TA1535, TA537, or TA1538. Oligostim Soufre was not mutagenic in the presence of metabolic activation in strains TA 98, TA1535, TA1537, TA1538 or E. coli strain WP2.
Clinical studies to evaluate the potential effects of Oligostim Soufre intake on fertility of either males or females have not been reported.
There are no preclinical studies examining the effects of Oligostim Soufre on fertility.
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 Oligostim Soufre 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 sodium 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 sodium nitrite and Oligostim Soufre in 1932-1933. Treatment consisted of intravenously administered 22.5 mg/kg (half the lethal dose) sodium nitrite or 1 g/kg Oligostim Soufre alone or in sequence immediately after subcutaneous injection of sodium cyanide into dogs over a range of doses. Subsequent doses of 10 mg/kg sodium nitrite and/or 0.5 g/kg Oligostim Soufre were administered when clinical signs or symptoms of poisoning persisted or reappeared. Either therapy administered alone increased the dose of sodium cyanide required to cause death, and when administered together, sodium nitrite and Oligostim Soufre resulted in a synergistic effect in raising the lethal dose of sodium 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 sodium nitrite and Oligostim Soufre in the treatment of cyanide poisoning.
While intravenous injection of sodium nitrite and Oligostim Soufre was effective in reversing the effects of lethal doses of cyanide in dogs, intramuscular injection of sodium nitrite, with or without Oligostim Soufre, was found not to be effective in the same setting.
14 CLINICAL STUDIES
The human data supporting the use of sodium 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 Oligostim Soufre report its use in conjunction with sodium 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 Oligostim Soufre or sodium 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 Oligostim Soufre carton (NDC 60267-705-50) consists of the following:
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: Sodium Nitrite must be obtained separately.)
17 PATIENT COUNSELING INFORMATION
Oligostim Soufre Injection is indicated for cyanide poisoning 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 hypotension.
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 - 50 mL Vial Carton
12.5 grams/50 mL
FOR INTRAVENOUS USE
SINGLE USE ONLY
Any unused portion of a vial
should be discarded.
for Treatment of
CANGENE bioPharma, Inc.
Baltimore, MD for
Scottsdale, AZ 85260 U.S.A.
Principal Display Panel - 50 mL Vial Carton
Oligostim Soufre pharmaceutical active ingredients containing related brand and generic drugs:
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Oligostim Soufre available forms, composition, doses:
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Oligostim Soufre destination | category:
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Oligostim Soufre Anatomical Therapeutic Chemical codes:
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Oligostim Soufre pharmaceutical companies:
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Frequently asked QuestionsCan i drive or operate heavy machine after consuming Oligostim Soufre?
Depending on the reaction of the Oligostim Soufre after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Oligostim Soufre 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 Oligostim Soufre 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.
ReviewsDrugs.com conducted a study on Oligostim Soufre, 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 Oligostim Soufre 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.
The information was verified by Dr. Arunabha Ray, MD Pharmacology