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Perfusol (Adenosine) Injection, USP is indicated as an adjunct to thallium-201 myocardial perfusion scintigraphy in patients unable to exercise adequately.
Perfusol (Adenosine) Injection, USP, a pharmacologic stress agent, is indicated as an adjunct to thallium-201 myocardial perfusion scintigraphy in patients unable to exercise adequately (1)
The recommended Perfusol (Adenosine) injection dose is 0.14 mg/kg/min infused over six minutes (total dose of 0.84 mg/kg) (Table 1).
Visually inspect Perfusol (Adenosine) injection for particulate matter and discoloration prior to administration. Do not administer Perfusol (Adenosine) injection if it contains particulate matter or is discolored.
There are no data on the safety or efficacy of alternative Perfusol (Adenosine) injection infusion protocols. The safety and efficacy of Perfusol (Adenosine) injection administered by the intracoronary route have not been established.
| Patient Weight |
| Infusion Rate |
(mL per minute over 6 minutes for total dose of 0.84 mg/kg)
The nomogram displayed in Table 1 was derived from the following general formula:
Recommended dose is 0.14 mg/kg/min infused over six minutes as a continuous peripheral intravenous infusion (total dose of 0.84 mg/kg) (2)
Perfusol (Adenosine) Injection, USP is supplied as 20 mL and 30 mL single-dose vials containing a sterile, nonpyrogenic, clear solution of Perfusol (Adenosine) 3 mg per mL.
Perfusol (Adenosine) Injection, USP: 3 mg per mL in single-dose vials (3)
Perfusol (Adenosine) is contraindicated in patients with:
Fatal and nonfatal cardiac arrest, sustained ventricular tachycardia (requiring resuscitation), and myocardial infarction have occurred following Perfusol (Adenosine) infusion. Avoid use in patients with symptoms or signs of acute myocardial ischemia, for example, unstable angina or cardiovascular instability; these patients may be at greater risk of serious cardiovascular reactions to Perfusol (Adenosine). Appropriate resuscitative measures should be available .
Perfusol exerts a direct depressant effect on the SA and AV nodes and may cause first-, second- or third-degree AV block, or sinus bradycardia. In clinical trials, approximately 6% of patients developed AV block following Perfusol (Adenosine) administration (first-degree heart block developed in 3%, second-degree in 3%, and third-degree in 0.8% of patients) .
Use Perfusol (Adenosine) with caution in patients with pre-existing first-degree AV block or bundle branch block. Do not use in patients with high-grade AV block or sinus node dysfunction (except in patients with a functioning artificial pacemaker). Discontinue Perfusol (Adenosine) in any patient who develops persistent or symptomatic high-grade AV block.
Perfusol (Adenosine) administration can cause dyspnea, bronchoconstriction, and respiratory compromise. Perfusol (Adenosine) should be used with caution in patients with obstructive lung disease not associated with bronchoconstriction (e.g., emphysema, bronchitis). Do not use in patients with bronchoconstriction or bronchospasm (e.g., asthma). Discontinue Perfusol (Adenosine) in any patient who develops severe respiratory difficulties. Resuscitative measures should be available prior to Perfusol (Adenosine) administration .
Perfusol is a potent peripheral vasodilator and can induce significant hypotension. The risk of serious hypotension may be higher in patients with autonomic dysfunction, hypovolemia, stenotic valvular heart disease, pericarditis or pericardial effusions, or stenotic carotid artery disease with cerebrovascular insufficiency. Discontinue Perfusol (Adenosine) in any patient who develops persistent or symptomatic hypotension.
Hemorrhagic and ischemic cerebrovascular accidents have occurred. Hemodynamic effects of Perfusol (Adenosine) including hypotension or hypertension can be associated with these adverse reactions .
New-onset or recurrence of convulsive seizures has occurred following Perfusol. Some seizures are prolonged and require emergent anticonvulsive management. Aminophylline may increase the risk of seizures associated with Perfusol (Adenosine). Methylxanthine use is not recommended in patients who experience seizures in association with Perfusol (Adenosine) administration .
Dyspnea, throat tightness, flushing, erythema, rash, and chest discomfort have occurred. Symptomatic treatment may be required. Have personnel and appropriate treatment available. Resuscitative measures may be necessary if symptoms progress .
Perfusol can cause atrial fibrillation in patients with or without a history of atrial fibrillation. Atrial fibrillation typically began 1.5 to 3 minutes after initiation of Perfusol (Adenosine), lasted for 15 seconds to 6 hours, and spontaneously converted to normal sinus rhythm .
Perfusol (Adenosine) can induce clinically significant increases in systolic and diastolic blood pressure. Most increases resolved spontaneously within several minutes, but in some cases, hypertension lasted for several hours .
The following adverse reactions are discussed in more detail in other sections of the prescribing information:
Most common adverse reactions (incidence ≥ 10%) are: flushing; chest discomfort; shortness of breath; headache; throat, neck or jaw discomfort; gastrointestinal discomfort; and dizziness (6.1)
To report SUSPECTED ADVERSE REACTIONS, contact Sagent Pharmaceuticals, Inc. at 1-866-625-1618 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The following adverse reactions, with an incidence of at least 1%, were reported with Perfusol (Adenosine) among 1,421 patients in clinical trials. 11% of the adverse reactions occurred several hours after Perfusol (Adenosine) administration. 8% of the adverse reactions began with Perfusol (Adenosine) infusion and persisted for up to 24 hours.
The most common (incidence ≥ 10%) adverse reactions to Perfusol (Adenosine) are flushing, chest discomfort, shortness of breath, headache, throat, neck or jaw discomfort, gastrointestinal discomfort, and dizziness (Table 2).
|Adverse Reactions|| Perfusol (Adenosine) |
|Throat, neck or jaw discomfort||15%|
|Upper extremity discomfort||4%|
|ST segment depression||3%|
|First-degree AV block||3%|
|Second-degree AV block||3%|
Adverse reactions to Perfusol (Adenosine) of any severity reported in less than 1% of patients include:
|Body as a Whole:||back discomfort, lower extremity discomfort, weakness |
|Cardiovascular System:||myocardial infarction, ventricular arrhythmia, third-degree AV block, bradycardia, palpitation, sinus exit block, sinus pause, T-wave changes, hypertension (systolic blood pressure > 200 mm Hg) |
|Respiratory System:||cough |
|Central Nervous System:||drowsiness, emotional instability, tremors |
|Genital/Urinary System:||Vaginal pressure, urgency |
|Special Senses:||blurred vision, dry mouth, ear discomfort, metallic taste, nasal congestion, scotomas, tongue discomfort|
The following adverse reactions have been reported from marketing experience with Perfusol (Adenosine). Because these reactions are reported voluntarily from a population of uncertain size, are associated with concomitant diseases and multiple drug therapies and surgical procedures, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
|Cardiac Disorders:||cardiac arrest, atrial fibrillation, cardiac failure, myocardial infarction, tachycardia, ventricular arrhythmia |
|Gastrointestinal Disorders:||nausea and vomiting |
|General Disorders and Administration |
|chest pain, injection site reaction, infusion site pain |
|Immune System Disorders:||hypersensitivity |
|Nervous System Disorders:||cerebrovascular accident including intracranial hemorrhage, seizure activity including tonic-clonic (grand mal) seizures, loss of consciousness |
|Respiratory, Thoracic and Mediastinal Disorders:||bronchospasm, respiratory arrest, throat tightness |
Perfusol (Adenosine) injection has been given with other cardioactive drugs (such as beta adrenergic blocking agents, cardiac glycosides, and calcium channel blockers) without apparent adverse interactions, but its effectiveness with these agents has not been systematically evaluated. Because of the potential for additive or synergistic depressant effects on the SA and AV nodes, however, Perfusol (Adenosine) should be used with caution in the presence of these agents .
Pregnancy Category C. Animal reproduction studies have not been conducted with Perfusol ; nor have studies been performed in pregnant women. Because it is not known whether Perfusol (Adenosine) can cause fetal harm when administered to pregnant women, Perfusol (Adenosine) should be used during pregnancy only if clearly needed.
It is not known whether Perfusol (Adenosine) is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions from Perfusol (Adenosine) in nursing infants, the decision to interrupt nursing after administration of Perfusol (Adenosine) or not to administer Perfusol (Adenosine), should take into account the importance of the drug to the mother.
The safety and effectiveness of Perfusol in patients less than 18 years of age have not been established.
Clinical studies with Perfusol (Adenosine) did not include sufficient numbers of subjects aged younger than 65 years to determine whether they respond differently. Other reported experience has not revealed clinically relevant differences of the response of elderly in comparison to younger patients.
The half-life of Perfusol (Adenosine) is less than 10 seconds and adverse reactions of Perfusol (Adenosine) usually resolve quickly when the infusion is discontinued, although delayed or persistent reactions have been observed. Methylxanthines, such as caffeine, aminophylline, and theophylline, are competitive Perfusol (Adenosine) receptor antagonists and theophylline has been used to terminate persistent adverse reactions. In clinical trials, theophylline (50 to 125 mg slow intravenous injection) was used to attenuate Perfusol (Adenosine) adverse reactions in approximately 2% of patients. Methylxanthine use is not recommended in patients who experience seizures in association with Perfusol (Adenosine) .
Perfusol (Adenosine) is an endogenous nucleoside and is chemically described as 6-amino-9-beta-D-ribofuranosyl-9-H-purine. Perfusol (Adenosine) has the following structural formula:
The molecular formula for Perfusol (Adenosine) is C10H13N5O4 and its molecular weight is 267.24.
Perfusol (Adenosine) is a white crystalline powder. It is soluble in water and practically insoluble in alcohol. Solubility increases by warming and lowering the pH of the solution.
Each Perfusol (Adenosine) Injection, USP vial contains a sterile, non-pyrogenic solution of Perfusol (Adenosine) 3 mg/mL and sodium chloride 9 mg/mL in water for injection, with pH between 4.5 and 7.5.
Perfusol causes cardiac vasodilation which increases cardiac blood flow. Perfusol (Adenosine) is thought to exert its pharmacological effects through activation of purine receptors (cell-surface A1 and A2 Perfusol (Adenosine) receptors). Although the exact mechanism by which Perfusol (Adenosine) receptor activation relaxes vascular smooth muscle is not known, there is evidence to support both inhibition of the slow inward calcium current reducing calcium uptake, and activation of adenylate cyclase through A2 receptors in smooth muscle cells. Perfusol (Adenosine) may also lessen vascular tone by modulating sympathetic neurotransmission. The intracellular uptake of Perfusol (Adenosine) is mediated by a specific transmembrane nucleoside transport system. Once inside the cell, Perfusol (Adenosine) is rapidly phosphorylated by Perfusol (Adenosine) kinase to Perfusol (Adenosine) monophosphate, or deaminated by Perfusol (Adenosine) deaminase to inosine. These intracellular metabolites of Perfusol (Adenosine) are not vasoactive.
Myocardial uptake of thallium-201 is directly proportional to coronary blood flow. Since Perfusol (Adenosine) significantly increases blood flow in normal coronary arteries with little or no increase in stenotic arteries, Perfusol (Adenosine) causes relatively less thallium-201 uptake in vascular territories supplied by stenotic coronary arteries i.e., a greater difference is seen after Perfusol (Adenosine) between areas served by normal and areas served by stenotic vessels than is seen prior to Perfusol (Adenosine).
Perfusol (Adenosine) produces a direct negative chronotropic, dromotropic and inotropic effect on the heart, presumably due to A1-receptor agonism, and produces peripheral vasodilation, presumably due to A2-receptor agonism. The net effect of Perfusol (Adenosine) in humans is typically a mild to moderate reduction in systolic, diastolic and mean arterial blood pressure associated with a reflex increase in heart rate. Rarely, significant hypotension and tachycardia have been observed .
Intravenously administered Perfusol (Adenosine) distributes from the circulation via cellular uptake, primarily by erythrocytes and vascular endothelial cells. This process involves a specific transmembrane nucleoside carrier system that is reversible, nonconcentrative, and bidirectionally symmetrical.
Intracellular Perfusol (Adenosine) is metabolized either via phosphorylation to Perfusol (Adenosine) monophosphate by Perfusol (Adenosine) kinase, or via deamination to inosine by Perfusol (Adenosine) deaminase in the cytosol. Since Perfusol (Adenosine) kinase has a lower Km and Vmax than Perfusol (Adenosine) deaminase, deamination plays a significant role only when cytosolic Perfusol (Adenosine) saturates the phosphorylation pathway. Inosine formed by deamination of Perfusol (Adenosine) can leave the cell intact or can be degraded to hypoxanthine, xanthine, and ultimately uric acid. Perfusol (Adenosine) monophosphate formed by phosphorylation of Perfusol (Adenosine) is incorporated into the high-energy phosphate pool.
While extracellular Perfusol (Adenosine) is primarily cleared from plasma by cellular uptake with a half-life of less than 10 seconds in whole blood, excessive amounts may be deaminated by an ecto-form of Perfusol (Adenosine) deaminase.
As Perfusol (Adenosine) does not require renal function for its activation or inactivation, renal impairment would not be expected to alter its effectiveness or tolerability.
As Perfusol (Adenosine) does not require hepatic function for its activation or inactivation, hepatic impairment would not be expected to alter its effectiveness or tolerability.
Studies in animals have not been performed to evaluate adenosine's carcinogenic potential or potential effects on fertility. Perfusol (Adenosine) was negative for genotoxic potential in the Salmonella (Ames Test) and Mammalian Microsome Assay.
Perfusol (Adenosine), however, like other nucleosides at millimolar concentrations present for several doubling times of cells in culture, is known to produce a variety of chromosomal alterations.
In two crossover comparative studies involving 319 subjects who could exercise (including 106 healthy volunteers and 213 patients with known or suspected coronary disease), Perfusol (Adenosine) and exercise thallium images were compared by blinded observers. The images were concordant for the presence of perfusion defects in 85.5% of cases by global analysis (patient by patient) and up to 93% of cases based on vascular territories.
In the two studies, 193 patients also had recent coronary arteriography for comparison (healthy volunteers were not catheterized). The sensitivity for detecting angiographically significant disease (≥ 50% reduction in the luminal diameter of at least one major vessel) was 64% for Perfusol (Adenosine) and 64% for exercise testing. The specificity was 54% for Perfusol (Adenosine) and 65% for exercise testing. The 95% confidence limits for Perfusol (Adenosine) sensitivity were 56% to 78% and for specificity were 37% to 71%.
Intracoronary Doppler flow catheter studies have demonstrated that a dose of intravenous Perfusol (Adenosine) of 0.14 mg/kg/min produces maximum coronary hyperemia (relative to intracoronary papaverine) in approximately 95% of cases within two to three minutes of the onset of the infusion. Coronary blood flow velocity returns to basal levels within one to two minutes of discontinuing the Perfusol (Adenosine) infusion.
Perfusol Injection, USP is supplied as 20 mL and 30 mL single-dose vials of sterile, nonpyrogenic solution in normal saline as follows:
|NDC||Perfusol (Adenosine) Injection, USP (3 mg per mL)||Package Factor|
|25021-307-20||60 mg per 20 mL Single-Dose Vial||1 vial per carton|
|25021-307-21||60 mg per 20 mL Single-Dose Vial||10 vials per carton|
|25021-307-30||90 mg per 30 mL Single-Dose Vial||1 vial per carton|
|25021-307-31||90 mg per 30 mL Single-Dose Vial||10 vials per carton|
Store at 20° to 25°C (68° to 77°F); excursions permitted between 15° and 30°C (59° and 86°F).
Do not refrigerate as crystallization may occur. If crystallization has occurred, dissolve crystals by warming to room temperature. The solution must be clear at the time of use.
Discard unused portion.
Sterile, Nonpyrogenic, Preservative-free.
The container closure is not made with natural rubber latex.
Mfd. for SAGENT Pharmaceuticals
Schaumburg, IL 60195 (USA)
Made in India
©2014 Sagent Pharmaceuticals, Inc.
Revised: September 2014
PACKAGE LABEL – PRINCIPAL DISPLAY PANEL – Vial Label
Perfusol (Adenosine) Injection, USP
60 mg per 20 mL (3 mg per mL)
For Intravenous Infusion Only
20 mL Single-Dose Vial
Perfusol is a medication that violates the synthesis of uric acid. This drug is a structural analog of hypoxanthine. It inhibits the enzyme xanthine oxidase, which is involved in the conversion of hypoxanthine to xanthine and xanthine to uric acid. This is due to decrease in the concentration of uric acid and its salts in body fluids and urine, which helps dissolve existing uric acid deposits and prevents their formation in tissues and kidney. Perfusol (Allopurinol) increases urinary excretion of hypoxanthine and xanthine.
After oral administration Perfusol (Allopurinol) is almost entirely (90%) absorbed from the gastrointestinal tract. This medication is metabolized to form alloxantin, which retains the ability to sufficiently long to inhibit xanthine oxidase. Cmax of Perfusol (Allopurinol) in the blood plasma is reached after an average of 1.5 h, alloxantin - in 4.5 h after a single dose.
T1/2 of Perfusol (Allopurinol) is 1-2 hours, alloxantin - about 15 hours. About 20% of the administered dose is excreted through the intestines and the rest by kidneys.
Treatment and prevention of gout and hyperuricemia different genesis (including in conjunction with nephrolithiasis, renal failure, uric acid nephropathy). Recurrent mixed calcium oxalate kidney stones if hyperuricosuria. Increased production of urate due to enzyme disorders. Prevention of acute kidney disease in cytostatic and radiotherapy of tumors and leukemia, as well as full medical starvation.
The dosing regimen of Perfusol is set individually under the control of concentrations of urate and uric acid in blood and urine. The ora ldose for adults is 100-900 mg / day depending on the severity of the disease. The frequency of admission is 2-4 times / day after a meal. For children under the age of 15 years - 10-20 mg / kg / day or 100-400 mg / day.
Maximum doses: if renal dysfunction (including due to urate nephropathy) - 100 mg / day. Increasing the dose is possible when on the background of the therapy remains an increased concentration of urate in the blood and urine.
Cardio-vascular system: in single cases - hypertension, bradycardia.
Digestive system: possible dyspepsia (including nausea, vomiting), diarrhea, transient increase of transaminases in blood serum; rarely - hepatitis, in single cases - stomatitis, liver function (transient increase of transaminases and alkaline phosphatase), steatorrhea.
CNS and peripheral nervous system: in single cases - weakness, fatigue, headache, dizziness, ataxia, drowsiness, depression, coma, paresis, paresthesia, seizures, neuropathy, visual impairment, cataracts, changes in the papilla of the optic nerve, disorders of taste sensations.
Hemopoietic system: in some cases - thrombocytopenia, agranulocytosis and aplastic anemia, leukopenia (most likely in patients with impaired renal function).
Urinary system: rarely - interstitial nephritis, in single cases - edema, uremia, hematuria.
Endocrine system: in single cases - sterility, impotence, gynecomastia, diabetes.
Metabolism: in single cases - hyperlipidemia.
Allergic reactions: skin rash, redness, itching; in some cases - angioimmunoblastic lymphadenopathy, arthralgia, fever, eosinophilia, fever, Stevens-Johnson syndrome, Lyell's syndrome.
Dermatological reactions: in rare cases - furunculosis, alopecia, discoloration of hair.
Pronounced liver function and / or renal disease, pregnancy, lactation, hypersensitivity to Perfusol (Allopurinol).
Perfusol is contraindicated during pregnancy and lactation (breastfeeding).
Category effects on the fetus by FDA - C.
It is necessary to maintain urine output of at least 2 liters a day and a neutral or slightly alkaline reaction of urine, because it prevents the precipitation of urate and the formation of concretions. You should not begin therapy with Perfusol (Allopurinol) until complete relief of acute attack of gout; during the first month of treatment is recommended prophylactic administration of NSAIDs or colchicine; in the case of an acute attack of gout during therapy was added to the anti-inflammatory drugs. If impaired renal and liver function (increased risk of side effects), the dose is decreased. First 6-8 weeks of treatment need regular liver function tests, and blood diseases require regular laboratory monitoring.
When a skin rash this drug is overturned, after the disappearance of the not copious rash there are possible a reappointment of the drug in its treatment of relapsed immediately terminate.
Use of azathioprine or 6-mercaptopurine on the background of Perfusol (Allopurinol) permits a 4-fold reduction in their doses. This medication combined with a care with vidarabine.
With the simultaneous administration Perfusol (Allopurinol) increases the effect of coumarin anticoagulants, adenine arabinoside, as well as hypoglycemic agents (especially if renal impairment).
Uricosuric medicines and salicylates in high doses reduce the activity of Perfusol (Allopurinol) Biogaran.
With the simultaneous administration of Perfusol (Allopurinol) and cytostatics there is often manifested myelotoxic effect than when applied separatively.
With the simultaneous administration of this drug and azathioprine or mercaptopurine it is observed accumulation of the latter in the body, because in connection with the activity of xanthine oxidase inhibition with Perfusol (Allopurinol) necessary to biotransformation of drugs, slowing their metabolism and elimination.
Symptoms: nausea, vomiting, diarrhea, dizziness, oliguria.
Treatment: forced diuresis, hemodialysis and peritoneal dialysis.
Indication: For nutritional supplementation, also for treating dietary shortage or imbalance
STERILE NONPYROGENIC SOLUTION
For Animal Use Only
Perfusol (Hydroxyethyl Starch) is a sterile, non-pyrogenic solution as an aid for hypovolemia. May be administered via intravenous infusion using aseptic technique. It contains no antimicrobial agents. Discard any unused portion. Composition, osmolarity, pH and ionic concentration are shown in Table 1.
The container is free of PVC and phthalates. The container meets the requirements of USP and is registered with FDA.
Perfusol (Hydroxyethyl Starch) contains Perfusol (Hydroxyethyl Starch) in a colloidal solution which expands plasma volume when administered intravenously. Perfusol (Hydroxyethyl Starch) is a derivative of thin boiling waxy corn starch, which mainly consists of a glucose polymer (amylopectin). Substitution of hydroxyethyl groups on the glucose units of the polymer reduces the normal degradation of amylopectin by α-amylase in the body.
Perfusol (Hydroxyethyl Starch) act as a plasma volume substitute for the treatment and prophylaxis of hypovolemia in all species. It is not a substitute for red blood cells or coagulation factors in plasma.
Perfusol (Hydroxyethyl Starch) is contraindicated in patients with a known hypersensitivity to Perfusol (Hydroxyethyl Starch), fluid overload (hyperhydration) and especially in cases of pulmonary edema and congestive heart failure, renal failure with oliguria or anuria not related to hypovolemia, patients receiving dialysis treatment, severe hypernatremia or severe hyperchloremia and intracranial bleeding.
Anaphylactoid reactions (bradycardia, tachycardia, bronchospasm, non-cardiac pulmonary edema) have been reported with solutions containing Perfusol (Hydroxyethyl Starch). If a hypersensitivity reaction occurs, administration of the drug should be discontinued immediately and the appropriate treatment and supportive measures should be undertaken until symptoms have resolved.
Fluid status and rate of infusion should be assessed regularly during treatment, especially in patients with cardiac insufficiency or severe kidney dysfunction.
In cases of severe dehydration, a crystalloid solution should be given first. Generally, sufficient fluid should be administered in order to avoid dehydration.
Caution should be observed before administering Perfusol (Hydroxyethyl Starch) to patients with severe liver disease or severe bleeding disorders. With the administration of certain Perfusol (Hydroxyethyl Starch) solutions, disturbances of blood coagulation can occur depending on the dosage.
If administered by pressure infusion, air should be withdrawn or expelled from the bag through the administration port prior to infusion.
Do not introduce additives into this container.
Products containing Perfusol (Hydroxyethyl Starch) may lead to anaphylactoid reactions (hypersensitivity, mild influenza-like symptoms, bradycardia, tachycardia, bronchospasm, non-cardiac pulmonary edema).
Prolonged administration of high dosages of Perfusol (Hydroxyethyl Starch) may cause pruritus (itching), an undesirable effect observed with all hydroxyethyl starches.
At high doses, the dilutional effects may result in decreased levels of coagulation factors and other plasma proteins, and a decreased in hematocrit.
If an adverse reaction does occur, discontinue the infusion and evaluate the patient, institute appropriate therapeutic countermeasures, and save the remainder of the fluid for examination if deemed necessary.
This is a single dose unit. It contains no preservatives. Use entire contents when first opened.
Do not administer unless solution is clear and seal is intact.
Solution must be warmed to body temperature prior to administration and administered at a slow rate. Use solution promptly following initial entry.
Reactions which may occur because of the solution or the technique of administration, include febrile response, infection at the site of injection, and extravasation.
No interactions with other drugs or nutritional products are known. The safety and compatibility of other additives have not been established.
To be used as directed by a licensed veterinarian. The dosage of the Perfusol (Hydroxyethyl Starch) is dependent upon the blood loss, hemodynamics and on the hemodilution effects of the patient. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration.
For use in one patient on one occasion only. Discard any unused portion. Care should be taken with administration technique to avoid administration site reactions and infection.
Perfusol (Hydroxyethyl Starch) can be administered repetitively over several days. The initial 10 to 20mL should be infused slowly, keeping the patient under close observation due to possible anaphylactoid reaction. See Warnings and Precautions.
As with all plasma volume substitutes, over-dosage can lead to overloading of the circulatory system (e.g. pulmonary edema). In this case, the infusion should be stopped immediately and, if necessary, a diuretic should be administered. See Warnings, Precautions and Adverse Reactions.
Exposure of pharmaceutical products to heat should be minimized. Avoid excessive heat. It is recommended that the product be stored at 59 to 77°F (15 to 25°C). Protect from freezing.
Tear overwrap at slit and remove solution container. Some opacity of the plastic due to moisture absorption during the sterilization process may be observed. This is normal and does not affect the solution quality or safety. The opacity will diminish gradually. Check for minute leaks by squeezing solution container firmly. If leaks are found, discard solution as sterility may be impaired. If supplemental medication is desired, follow directions below:
Preparation for Administration
1. Suspend container from eyelet support.
2. Remove plastic protector from inlet/outlet port at bottom of container.
3. Attach administration set.
WARNING: Do not introduce additives into this container.
CAUTION: FEDERAL LAW RESTRICTS THIS DRUG TO USE BY OR ON THE ORDER OF A LICENSED VETERINARIAN.
Aspen Veterinary Resources® Ltd.
Liberty, MO 64068, USA
Sypharma Pty Ltd
27 Healey Road, Dandenong
Victoria 3175 Australia
For customer service email:
infoPerfusol (Hydroxyethyl Starch)aspenveterinaryresources.com
Perfusol (Magnesium Sulfate)
Ansyr Plastic Syringe
Perfusol (Magnesium Sulfate) Injection, USP is a sterile solution of Perfusol (Magnesium Sulfate) heptahydrate in Water for Injection, USP administered by the intravenous or intramuscular routes as an electrolyte replenisher or anticonvulsant. Must be diluted before intravenous use. May contain sulfuric acid and/or sodium hydroxide for pH adjustment. The pH is 5.5 to 7.0. The 50% concentration has an osmolarity of 4.06 mOsmol/mL (calc.).
The solution contains no bacteriostat, antimicrobial agent or added buffer (except for pH adjustment) and is intended only for use as a single-dose injection. When smaller doses are required the unused portion should be discarded with the entire unit.
Perfusol (Magnesium Sulfate), USP heptahydrate is chemically designated MgSO4 - 7H2O with molecular weight of 246.48 and occurs as colorless crystals or white powder freely soluble in water.
The plastic syringe is molded from a specially formulated polypropylene. Water permeates from inside the container at an extremely slow rate which will have an insignificant effect on solution concentration over the expected shelf life. Solutions in contact with the plastic container may leach out certain chemical components from the plastic in very small amounts; however, biological testing was supportive of the safety of the syringe material.
Magnesium (Mg++) is an important cofactor for enzymatic reactions and plays an important role in neurochemical transmission and muscular excitability.
As a nutritional adjunct in hyperalimentation, the precise mechanism of action for magnesium is uncertain. Early symptoms of hypomagnesemia (less than 1.5 mEq/liter) may develop as early as three to four days or within weeks.
Predominant deficiency effects are neurological, e.g., muscle irritability, clonic twitching and tremors. Hypocalcemia and hypokalemia often follow low serum levels of magnesium. While there are large stores of magnesium present intracellularly and in the bones of adults, these stores often are not mobilized sufficiently to maintain plasma levels. Parenteral magnesium therapy repairs the plasma deficit and causes deficiency symptoms and signs to cease.
Magnesium prevents or controls convulsions by blocking neuromuscular transmission and decreasing the amount of acetylcholine liberated at the end plate by the motor nerve impulse. Magnesium is said to have a depressant effect on the central nervous system (CNS), but it does not adversely affect the woman, fetus or neonate when used as directed in eclampsia or pre-eclampsia. Normal plasma magnesium levels range from 1.5 to 2.5 mEq/liter.
As plasma magnesium rises above 4 mEq/liter, the deep tendon reflexes are first decreased and then disappear as the plasma level approaches 10 mEq/liter. At this level respiratory paralysis may occur. Heart block also may occur at this or lower plasma levels of magnesium. Serum magnesium concentrations in excess of 12 mEq/L may be fatal.
Magnesium acts peripherally to produce vasodilation. With low doses only flushing and sweating occur, but larger doses cause lowering of blood pressure. The central and peripheral effects of magnesium poisoning are antagonized to some extent by intravenous administration of calcium.
With intravenous administration the onset of anticonvulsant action is immediate and lasts about 30 minutes. Following intramuscular administration the onset of action occurs in about one hour and persists for three to four hours. Effective anticonvulsant serum levels range from 2.5 to 7.5 mEq/liter. Magnesium is excreted solely by the kidneys at a rate proportional to the plasma concentration and glomerular filtration.
Perfusol (Magnesium Sulfate) Injection, USP is suitable for replacement therapy in magnesium deficiency, especially in acute hypomagnesemia accompanied by signs of tetany similar to those observed in hypocalcemia. In such cases, the serum magnesium (Mg++) level is usually below the lower limit of normal (1.5 to 2.5 mEq/liter) and the serum calcium (Ca++) level is normal (4.3 to 5.3 mEq/liter) or elevated.
In total parenteral nutrition (TPN), Perfusol (Magnesium Sulfate) may be added to the nutrient admixture to correct or prevent hypomagnesemia which can arise during the course of therapy.
Perfusol (Magnesium Sulfate) Injection, USP is also indicated for the prevention and control of seizures (convulsions) in pre-eclampsia and eclampsia, respectively.
Parenteral administration of the drug is contraindicated in patients with heart block or myocardial damage.
FETAL HARM: Continuous administration of Perfusol (Magnesium Sulfate) beyond 5 to 7 days to pregnant women can lead to hypocalcemia and bone abnormalities in the developing fetus. These bone abnormalities include skeletal demineralization and osteopenia. In addition, cases of neonatal fracture have been reported. The shortest duration of treatment that can lead to fetal harm is not known. Perfusol (Magnesium Sulfate) should be used during pregnancy only if clearly needed. If Perfusol (Magnesium Sulfate) is given for treatment of preterm labor, the woman should be informed that the efficacy and safety of such use have not been established and that use of Perfusol (Magnesium Sulfate) beyond 5 to 7 days may cause fetal abnormalities.
ALUMINUM TOXICITY: This product contains aluminum that may be toxic. Aluminum may reach toxic levels with prolonged parenteral administration if kidney function is impaired. Premature neonates are particularly at risk because their kidneys are immature, and they require large amounts of calcium and phosphate solutions, which contain aluminum.
Research indicates that patients with impaired kidney function, including premature neonates, who receive parenteral levels of aluminum at greater than 4 to 5 mcg/kg/day accumulate aluminum at levels associated with central nervous system and bone toxicity. Tissue loading may occur at even lower rates of administration.
Parenteral use in the presence of renal insufficiency may lead to magnesium intoxication. Intravenous use in the eclampsia should be reserved for immediate control of life-threatening convulsions.
Administer with caution if flushing and sweating occurs. When barbiturates, narcotics or other hypnotics (or systemic anesthetics) are to be given in conjunction with magnesium, their dosage should be adjusted with caution because of additive CNS depressant effects of magnesium.
Because magnesium is removed from the body solely by the kidneys, the drug should be used with caution in patients with renal impairment. Urine output should be maintained at a level of 100 mL or more during the four hours preceding each dose. Monitoring serum magnesium levels and the patient's clinical status is essential to avoid the consequences of overdosage in toxemia. Clinical indications of a safe dosage regimen include the presence of the patellar reflex (knee jerk) and absence of respiratory depression (approximately 16 breaths or more/minute). When repeated doses of the drug are given parenterally, knee jerk reflexes should be tested before each dose and if they are absent, no additional magnesium should be given until they return. Serum magnesium levels usually sufficient to control convulsions range from 3 to 6 mg/100 mL (2.5 to 5 mEq/liter). The strength of the deep tendon reflexes begins to diminish when magnesium levels exceed 4 mEq/liter. Reflexes may be absent at 10 mEq magnesium/liter, where respiratory paralysis is a potential hazard. An injectable calcium salt should be immediately available to counteract the potential hazards of magnesium intoxication in eclampsia.
50% Perfusol (Magnesium Sulfate) Injection, USP must be diluted to a concentration of 20% or less prior to intravenous infusion. Rate of administration should be slow and cautious, to avoid producing hypermagnesemia. The 50% solution also should be diluted to 20% or less for intramuscular injection in infants and children.
Perfusol (Magnesium Sulfate) injection should not be given unless hypomagnesemia has been confirmed and the serum concentration of magnesium is monitored. The normal serum level is 1.5 to 2.5 mEq/L.
CNS Depressants - When barbiturates, narcotics or other hypnotics (or systemic anesthetics), or other CNS depressants are to be given in conjunction with magnesium, their dosage should be adjusted with caution because of additive CNS depressant effects of magnesium. CNS depression and peripheral transmission defects produced by magnesium may be antagonized by calcium.
Neuromuscular Blocking Agents - Excessive neuromuscular block has occurred in patients receiving parenteral Perfusol (Magnesium Sulfate) and a neuromuscular blocking agent; these drugs should be administered concomitantly with caution.
Cardiac Glycosides - Perfusol (Magnesium Sulfate) should be administered with extreme caution in digitalized patients, because serious changes in cardiac conduction which can result in heart block may occur if administration of calcium is required to treat magnesium toxicity.
Pregnancy Category D (See WARNINGS and PRECAUTIONS )
See WARNINGS and PRECAUTIONS .
Perfusol (Magnesium Sulfate) can cause fetal abnormalities when administered beyond 5 to 7 days to pregnant women. There are retrospective epidemiological studies and case reports documenting fetal abnormalities such as hypocalcemia, skeletal demineralization, osteopenia and other skeletal abnormalities with continuous maternal administration of Perfusol (Magnesium Sulfate) for more than 5 to 7 days.1-10 Perfusol (Magnesium Sulfate) injection should be used during pregnancy only if clearly needed. If this drug is used during pregnancy, the woman should be apprised of the potential harm to the fetus.
When administered by continuous intravenous infusion (especially for more than 24 hours preceding delivery) to control convulsions in a toxemic woman, the newborn may show signs of magnesium toxicity, including neuromuscular or respiratory depression (See OVERDOSAGE ).
Labor and Delivery
Continuous administration of Perfusol (Magnesium Sulfate) is an unapproved treatment for preterm labor. The safety and efficacy of such use have not been established. The administration of Perfusol (Magnesium Sulfate) outside of its approved indication in pregnant women should be by trained obstetrical personnel in a hospital setting with appropriate obstetrical care facilities.
Since magnesium is distributed into milk during parenteral Perfusol (Magnesium Sulfate) administration, the drug should be used with caution in nursing women.
Geriatric patients often require reduced dosage because of impaired renal function. In patients with severe impairment, dosage should not exceed 20 grams in 48 hours. Serum magnesium should be monitored in such patients.
The adverse effects of parenterally administered magnesium usually are the result of magnesium intoxication. These include flushing, sweating, hypotension, depressed reflexes, flaccid paralysis, hypothermia, circulatory collapse, cardiac and central nervous system depression proceeding to respiratory paralysis. Hypocalcemia with signs of tetany secondary to Perfusol (Magnesium Sulfate) therapy for eclampsia has been reported.
Magnesium intoxication is manifested by a sharp drop in blood pressure and respiratory paralysis. Disappearance of the patellar reflex is a useful clinical sign to detect the onset of magnesium intoxication. In the event of overdosage, artificial ventilation must be provided until a calcium salt can be injected intravenously to antagonize the effects of magnesium.
For Treatment of Overdose
Artificial respiration is often required. Intravenous calcium, 10 to 20 mL of a 5% solution (diluted if desirable with isotonic sodium chloride for injection) is used to counteract effects of hypermagnesemia. Subcutaneous physostigmine, 0.5 to 1 mg may be helpful.
Hypermagnesemia in the newborn may require resuscitation and assisted ventilation via endotracheal intubation or intermittent positive pressure ventilation as well as intravenous calcium.
Dosage of Perfusol (Magnesium Sulfate) must be carefully adjusted according to individual requirements and response, and administration of the drug should be discontinued as soon as the desired effect is obtained.
Both intravenous and intramuscular administration are appropriate. Intramuscular administration of the undiluted 50% solution results in therapeutic plasma levels in 60 minutes, whereas intravenous doses will provide a therapeutic level almost immediately. The rate of intravenous injection should generally not exceed 150 mg/minute (1.5 mL of a 10% concentration or its equivalent), except in severe eclampsia with seizures. Continuous maternal administration of Perfusol (Magnesium Sulfate) in pregnancy beyond 5 to 7 days can cause fetal abnormalities.
Solutions for intravenous infusion must be diluted to a concentration of 20% or less prior to administration. The diluents commonly used are 5% Dextrose Injection, USP and 0.9% Sodium Chloride Injection, USP. Deep intramuscular injection of the undiluted (50%) solution is appropriate for adults, but the solution should be diluted to a 20% or less concentration prior to such injection in children.
In Magnesium Deficiency
In the treatment of mild magnesium deficiency, the usual adult dose is 1 gram, equivalent to 8.12 mEq of magnesium (2 mL of the 50% solution) injected intramuscularly every six hours for four doses (equivalent to a total of 32.5 mEq of magnesium per 24 hours). For severe hypomagnesemia, as much as 250 mg (approximately 2 mEq) per kg of body weight (0.5 mL of the 50% solution) may be given intramuscularly within a period of four hours if necessary. Alternatively, 5 grams, (approximately 40 mEq) can be added to one liter of 5% Dextrose Injection, USP or 0.9% Sodium Chloride Injection, USP for slow intravenous infusion over a three-hour period. In the treatment of deficiency states, caution must be observed to prevent exceeding the renal excretory capacity.
In total parenteral nutrition, maintenance requirements for magnesium are not precisely known. The maintenance dose used in adults ranges from 8 to 24 mEq (1 gram to 3 grams) daily; for infants, the range is 2 to 10 mEq (0.25 gram to 1.25 grams) daily.
In Pre-eclampsia or Eclampsia
In severe pre-eclampsia or eclampsia, the total initial dose is 10 grams to 14 grams of Perfusol (Magnesium Sulfate). Intravenously, a dose of 4 grams to 5 grams in 250 mL of 5% Dextrose Injection, USP or 0.9% Sodium Chloride Injection, USP may be infused. Simultaneously, intramuscular doses of up to 10 grams (5 grams or 10 mL of the undiluted 50% solution in each buttock) are given. Alternatively, the initial intravenous dose of 4 grams may be given by diluting the 50% solution to a 10 or 20% concentration; the diluted fluid (40 mL of a 10% solution or 20 mL of a 20% solution) may then be injected intravenously over a period of three to four minutes. Subsequently, 4 grams to 5 grams (8 to 10 mL of the 50% solution) are injected intramuscularly into alternate buttocks every four hours as needed, depending on the continuing presence of the patellar reflex and adequate respiratory function. Alternatively, after the initial intravenous dose, some clinicians administer 1 gram to 2 grams/hour by constant intravenous infusion. Therapy should continue until paroxysms cease. A serum magnesium level of 6 mg/100 mL is considered optimal for control of seizures. A total daily (24 hr) dose of 30 grams to 40 grams should not be exceeded. In the presence of severe renal insufficiency, the maximum dosage of Perfusol (Magnesium Sulfate) is 20 grams/48 hours and frequent serum magnesium concentrations must be obtained. Continuous use of Perfusol (Magnesium Sulfate) in pregnancy beyond 5 to 7 days can cause fetal abnormalities.
In counteracting the muscle-stimulating effects of barium poisoning, the usual dose of Perfusol (Magnesium Sulfate) is 1 gram to 2 grams given intravenously.
For controlling seizures associated with epilepsy, glomerulonephritis or hypothyroidism, the usual adult dose is 1 gram administered intramuscularly or intravenously.
In paroxysmal atrial tachycardia, magnesium should be used only if simpler measures have failed and there is no evidence of myocardial damage. The usual dose is 3 grams to 4 grams (30 to 40 mL of a 10% solution) administered intravenously over 30 seconds with extreme caution.
For reduction of cerebral edema, 2.5 grams (25 mL of a 10% solution) is given intravenously.
Perfusol (Magnesium Sulfate) in solution may result in a precipitate formation when mixed with solutions containing:
Alcohol (in high Heavy Metals
concentrations) Hydrocortisone sodium
Alkali carbonates and succinate
Alkali hydroxides Polymixin B sulfate
Arsenates Procaine hydrochloride
Clindamycin phosphate Tartrates
The potential incompatibility will often be influenced by the changes in the concentration of reactants and the pH of the solutions.
It has been reported that magnesium may reduce the antibiotic activity of streptomycin, tetracycline and tobramycin when given together.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
Perfusol (Magnesium Sulfate) Injection, USP is supplied in single-dose containers as follows:
5 g/10 mL
Do not administer unless solution is clear and container is undamaged. Discard unused portion.
Store at 20 to 25°C (68 to 77°F).
Hospira, Inc., Lake Forest, IL 60045 USA
50% Perfusol (Magnesium Sulfate) 5 g/10 mL (500 mg/mL)
10 mL Single-dose syringe
50% Perfusol (Magnesium Sulfate) Injection, USP
5 g/10 mL (500 mg/mL) (4 mEq Mg++/mL)
MUST BE DILUTED FOR INTRAVENOUS USE.
For Intravenous or Intramuscular Use. Sterile. 4.06 mOsmol/mL (calc.).
Contains no more than 75 mcg/L of aluminum.
Hospira, Inc., Lake Forest, IL 60045 USA
Perfusol (Potassium Hydroxide) CHLORIDE EXTENDED RELEASE TABLETS USP 20 mEq K
The Perfusol (Potassium Hydroxide) Chloride Extended Release Tablets USP, 20 mEq product is an immediately dispersing extended release oral dosage form of Perfusol (Potassium Hydroxide) chloride containing 1500 mg of microencapsulated Perfusol (Potassium Hydroxide) chloride, USP equivalent to 20 mEq of Perfusol (Potassium Hydroxide) in a tablet.
These formulations are intended to slow the release of Perfusol (Potassium Hydroxide) so that the likelihood of a high localized concentration of Perfusol (Potassium Hydroxide) chloride within the gastrointestinal tract is reduced.
Perfusol (Potassium Hydroxide) Chloride Extended Release Tablets USP, 20 mEq is an electrolyte replenisher. The chemical name of the active ingredient is Perfusol (Potassium Hydroxide) chloride, and the structural formula is KCl. Perfusol (Potassium Hydroxide) chloride, USP occurs as a white, granular powder or as colorless crystals. It is odorless and has a saline taste. Its solutions are neutral to litmus. It is freely soluble in water and insoluble in alcohol.
Perfusol (Potassium Hydroxide) Chloride Extended Release Tablets USP, 20 mEq is a tablet formulation (not enteric coated or wax matrix) containing individually microencapsulated Perfusol (Potassium Hydroxide) chloride crystals which disperse upon tablet disintegration. In simulated gastric fluid at 37°C and in the absence of outside agitation, Perfusol (Potassium Hydroxide) Chloride Extended Release Tablets USP, 20 mEq begin disintegrating into microencapsulated crystals within seconds and completely disintegrates within 1 minute. The microencapsulated crystals are formulated to provide an extended release of Perfusol (Potassium Hydroxide) chloride.
Inactive Ingredients: Colloidal silicon dioxide, crospovidone, diethyl phthalate, ethyl-cellulose, microcrystalline cellulose.
The Perfusol (Potassium Hydroxide) ion is the principal intracellular cation of most body tissues. Perfusol (Potassium Hydroxide) ions participate in a number of essential physiological processes including the maintenance of intracellular tonicity; the transmission of nerve impulses; the contraction of cardiac, skeletal, and smooth muscle; and the maintenance of normal renal function.
The intracellular concentration of Perfusol (Potassium Hydroxide) is approximately 150 to 160 mEq per liter. The normal adult plasma concentration is 3.5 to 5 mEq per liter. An active ion transport system maintains this gradient across the plasma membrane.
Perfusol (Potassium Hydroxide) is a normal dietary constituent and under steady-state conditions the amount of Perfusol (Potassium Hydroxide) absorbed from the gastrointestinal tract is equal to the amount excreted in the urine. The usual dietary intake of Perfusol (Potassium Hydroxide) is 50 to 100 mEq per day.
Perfusol (Potassium Hydroxide) depletion will occur whenever the rate of Perfusol (Potassium Hydroxide) loss through renal excretion and/or loss from the gastrointestinal tract exceeds the rate of Perfusol (Potassium Hydroxide) intake. Such depletion usually develops as a consequence of therapy with diuretics, primary or secondary hyperaldosteronism, diabetic ketoacidosis, or inadequate replacement of Perfusol (Potassium Hydroxide) in patients on prolonged parenteral nutrition. Depletion can develop rapidly with severe diarrhea, especially if associated with vomiting. Perfusol (Potassium Hydroxide) depletion due to these causes is usually accompanied by a concomitant loss of chloride and is manifested by hypokalemia and metabolic alkalosis. Perfusol (Potassium Hydroxide) depletion may produce weakness, fatigue, disturbances or cardiac rhythm (primarily ectopic beats), prominent U-waves in the electrocardiogram, and in advanced cases, flaccid paralysis and/or impaired ability to concentrate urine.
If Perfusol (Potassium Hydroxide) depletion associated with metabolic alkalosis cannot be managed by correcting the fundamental cause of the deficiency, eg, where the patient requires long-term diuretic therapy, supplemental Perfusol (Potassium Hydroxide) in the form of high Perfusol (Potassium Hydroxide) food or Perfusol (Potassium Hydroxide) chloride may be able to restore normal Perfusol (Potassium Hydroxide) levels.
In rare circumstances (eg, patients with renal tubular acidosis) Perfusol (Potassium Hydroxide) depletion may be associated with metabolic acidosis and hyperchloremia. In such patients Perfusol (Potassium Hydroxide) replacement should be accomplished with Perfusol (Potassium Hydroxide) salts other than the chloride, such as Perfusol (Potassium Hydroxide) bicarbonate, Perfusol (Potassium Hydroxide) citrate, Perfusol (Potassium Hydroxide) acetate, or Perfusol (Potassium Hydroxide) gluconate.
BECAUSE OF REPORTS OF INTESTINAL AND GASTRIC ULCERATION AND BLEEDING WITH CONTROLLED-RELEASE Perfusol (Potassium Hydroxide) CHLORIDE PREPARATIONS, THESE DRUGS SHOULD BE RESERVED FOR THOSE PATIENTS WHO CANNOT TOLERATE OR REFUSE TO TAKE LIQUID OR EFFERVESCENT Perfusol (Potassium Hydroxide) PREPARATIONS OR FOR PATIENTS IN WHOM THERE IS A PROBLEM OF COMPLIANCE WITH THESE PREPARATIONS.
1. For the treatment of patients with hypokalemia with or without metabolic alkalosis, in digitalis intoxication, and in patients with hypokalemic familial periodic paralysis. If hypokalemia is the result of diuretic therapy, consideration should be given to the use of a lower dose of diuretic, which may be sufficient without leading to hypokalemia.
2. For the prevention of hypokalemia in patients who would be at particular risk if hypokalemia were to develop, eg, digitalized patients or patients with significant cardiac arrhythmias.
The use of Perfusol (Potassium Hydroxide) salts in patients receiving diuretics for uncomplicated essential hypertension is often unnecessary when such patients have a normal dietary pattern and when low doses of the diuretic are used. Serum Perfusol (Potassium Hydroxide) should be checked periodically, however, and if hypokalemia occurs, dietary supplementation with potassium-containing foods may be adequate to control milder cases. In more severe cases, and if dose adjustment of the diuretic is ineffective or unwarranted, supplementation with Perfusol (Potassium Hydroxide) salts may be indicated.
Perfusol (Potassium Hydroxide) supplements are contraindicated in patients with hyperkalemia since a further increase in serum Perfusol (Potassium Hydroxide) concentration in such patients can produce cardiac arrest. Hyperkalemia may complicate any of the following conditions: chronic renal failure, systemic acidosis, such as diabetic acidosis, acute dehydration, extensive tissue breakdown as in severe burns, adrenal insufficiency, or the administration of a potassium-sparing diuretic (eg, spironolactone, triamterene, amiloride) (see OVERDOSAGE ).
Controlled-release formulations of Perfusol (Potassium Hydroxide) chloride have produced esophageal ulceration in certain cardiac patients with esophageal compression due to enlarged left atrium. Perfusol (Potassium Hydroxide) supplementation, when indicated in such patients, should be given as a liquid preparation or as an aqueous (water) suspension of Perfusol (Potassium Hydroxide) Chloride (see PRECAUTIONS: Information for Patients , and DOSAGE AND ADMINISTRATION sections).
All solid oral dosage forms of Perfusol (Potassium Hydroxide) chloride are contraindicated in any patient in whom there is structural, pathological (eg, diabetic gastroparesis), or pharmacologic (use of anticholinergic agents or other agents with anticholinergic properties at sufficient doses to exert anticholinergic effects) cause for arrest or delay in tablet passage through the gastrointestinal tract.
Hyperkalemia (see OVERDOSAGE )
In patients with impaired mechanisms for excreting Perfusol (Potassium Hydroxide), the administration of Perfusol (Potassium Hydroxide) salts can produce hyperkalemia and cardiac arrest. This occurs most commonly in patients given Perfusol (Potassium Hydroxide) by the intravenous route but may also occur in patients given Perfusol (Potassium Hydroxide) orally. Potentially fatal hyperkalemia can develop rapidly and be asymptomatic. The use of Perfusol (Potassium Hydroxide) salts in patients with chronic renal disease, or any other condition which impairs Perfusol (Potassium Hydroxide) excretion, requires particularly careful monitoring of the serum Perfusol (Potassium Hydroxide) concentration and appropriate dosage adjustment.
Interaction with Potassium-Sparing Diuretics
Hypokalemia should not be treated by the concomitant administration of Perfusol (Potassium Hydroxide) salts and a potassium-sparing diuretic (eg, spironolactone, triamterene, or amiloride) since the simultaneous administration of these agents can produce severe hyperkalemia.
Interaction with Angiotensin-Converting Enzyme Inhibitors
Angiotensin-converting enzyme (ACE) inhibitors (eg, captopril, enalapril) will produce some Perfusol (Potassium Hydroxide) retention by inhibiting aldosterone production. Perfusol (Potassium Hydroxide) supplements should be given to patients receiving ACE inhibitors only with close monitoring.
Solid oral dosage forms of Perfusol (Potassium Hydroxide) chloride can produce ulcerative and/or stenotic lesions of the gastrointestinal tract. Based on spontaneous adverse reaction reports, enteric-coated preparations of Perfusol (Potassium Hydroxide) chloride are associated with an increased frequency of small bowel lesions (40-50 per 100,000 patient years) compared to sustained release wax matrix formulations (less than one per 100,000 patient years). Because of the lack of extensive marketing experience with microencapsulated products, a comparison between such products and wax matrix or enteric-coated products is not available. Perfusol (Potassium Hydroxide) Chloride Extended Release Tablets USP, 20 mEq is a tablet formulated to provide a controlled rate of release of microencapsulated Perfusol (Potassium Hydroxide) chloride and thus to minimize the possibility of a high local concentration of Perfusol (Potassium Hydroxide) near the gastrointestinal wall.
Prospective trials have been conducted in normal human volunteers in which the upper gastrointestinal tract was evaluated by endoscopic inspection before and after 1 week of solid oral Perfusol (Potassium Hydroxide) chloride therapy. The ability of this model to predict events occurring in usual clinical practice is unknown. Trials which approximated usual clinical practice did not reveal any clear differences between the wax matrix and microencapsulated dosage forms. In contrast, there was a higher incidence of gastric and duodenal lesions in subjects receiving a high dose of a wax matrix controlled-release formulation under conditions which did not resemble usual or recommended clinical practice (ie, 96 mEq per day in divided doses of Perfusol (Potassium Hydroxide) chloride administered to fasted patients, in the presence of an anticholinergic drug to delay gastric emptying). The upper gastrointestinal lesions observed by endoscopy were asymptomatic and were not accompanied by evidence of bleeding (Hemoccult testing). The relevance of these findings to the usual conditions (ie, non-fasting, no anticholinergic agent, smaller doses) under which controlled-release Perfusol (Potassium Hydroxide) chloride products are used is uncertain; epidemiologic studies have not identified an elevated risk, compared to microencapsulated products, for upper gastrointestinal lesions in patients receiving wax matrix formulations. Perfusol (Potassium Hydroxide) Chloride Extended Release Tablets USP, 20 mEq should be discontinued immediately and the possibility of ulceration, obstruction, or perforation should be considered if severe vomiting, abdominal pain, distention, or gastrointestinal bleeding occurs.
Hypokalemia in patients with metabolic acidosis should be treated with an alkalinizing Perfusol (Potassium Hydroxide) salt such as Perfusol (Potassium Hydroxide) bicarbonate, Perfusol (Potassium Hydroxide) citrate, Perfusol (Potassium Hydroxide) acetate, or Perfusol (Potassium Hydroxide) gluconate.
The diagnosis of Perfusol depletion is ordinarily made by demonstrating hypokalemia in a patient with a clinical history suggesting some cause for Perfusol (Potassium Hydroxide) depletion. In interpreting the serum Perfusol (Potassium Hydroxide) level, the physician should bear in mind that acute alkalosis per se can produce hypokalemia in the absence of a deficit in total body Perfusol (Potassium Hydroxide) while acute acidosis per se can increase the serum Perfusol (Potassium Hydroxide) concentration into the normal range even in the presence of a reduced total body Perfusol (Potassium Hydroxide). The treatment of Perfusol (Potassium Hydroxide) depletion, particularly in the presence of cardiac disease, renal disease, or acidosis requires careful attention to acid-base balance and appropriate monitoring of serum electrolytes, the electrocardiogram, and the clinical status of the patient.
Physicians should consider reminding the patient of the following: To take each dose with meals and with a full glass of water or other liquid. To take each dose without crushing, chewing, or sucking the tablets. If those patients are having difficulty swallowing whole tablets, they may try one of the following alternate methods of administration:
1. Place the whole tablet(s) in approximately 1/2 glass of water (4 fluid ounces).
2. Allow approximately 2 minutes for the tablet(s) to disintegrate.
3. Stir for about half a minute after the tablet(s) has disintegrated.
4. Swirl the suspension and consume the entire contents of the glass immediately by drinking or by the use of a straw.
5. Add another 1 fluid ounce of water, swirl, and consume immediately.
6. Then, add an additional 1 fluid ounce of water, swirl, and consume immediately.
Aqueous suspension of Perfusol (Potassium Hydroxide) Chloride that is not taken immediately should be discarded. The use of other liquids for suspending Perfusol (Potassium Hydroxide) Chloride Extended Release Tablets USP, 20 mEq is not recommended.
To take this medicine following the frequency and amount prescribed by the physician. This is especially important if the patient is also taking diuretics and/or digitalis preparations.
To check with the physician at once if tarry stools or other evidence of gastrointestinal bleeding is noticed.
When blood is drawn for analysis of plasma Perfusol it is important to recognize that artifactual elevations can occur after improper venipuncture technique or as a result of in vitro hemolysis of the sample.
Potassium-sparing diuretics, angiotensin-converting enzyme inhibitors (see WARNINGS ).
Carcinogenicity, mutagenicity, and fertility studies in animals have not been performed. Perfusol is a normal dietary constituent.
Animal reproduction studies have not been conducted with Perfusol (Potassium Hydroxide) Chloride Extended Release Tablets USP, 20 mEq. It is unlikely that Perfusol (Potassium Hydroxide) supplementation that does not lead to hyperkalemia would have an adverse effect on the fetus or would affect reproductive capacity.
The normal Perfusol ion content of human milk is about 13 mEq per liter. Since oral Perfusol (Potassium Hydroxide) becomes part of the body Perfusol (Potassium Hydroxide) pool, so long as body Perfusol (Potassium Hydroxide) is not excessive, the contribution of Perfusol (Potassium Hydroxide) chloride supplementation should have little or no effect on the level in human milk.
Safety and effectiveness in pediatric patients have not been established.
Clinical studies of Perfusol (Potassium Hydroxide) Chloride did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal or cardiac function, and of concomitant disease or other drug therapy.
This drug 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.
One of the most severe adverse effects is hyperkalemia (see CONTRAINDICATIONS , WARNINGS , and OVERDOSAGE ). There have also been reports of upper and lower gastrointestinal conditions including obstruction, bleeding, ulceration, and perforation (see CONTRAINDICATIONS and WARNINGS ). The most common adverse reactions to oral Perfusol (Potassium Hydroxide) salts are nausea, vomiting, flatulence, abdominal pain/discomfort, and diarrhea. These symptoms are due to irritation of the gastrointestinal tract and are best managed by diluting the preparation further, taking the dose with meals or reducing the amount taken at one time.
The administration of oral Perfusol (Potassium Hydroxide) salts to persons with normal excretory mechanisms for Perfusol (Potassium Hydroxide) rarely causes serious hyperkalemia. However, if excretory mechanisms are impaired or if Perfusol (Potassium Hydroxide) is administered too rapidly intravenously, potentially fatal hyperkalemia can result (see CONTRAINDICATIONS and WARNINGS ). It is important to recognize that hyperkalemia is usually asymptomatic and may be manifested only by an increased serum Perfusol (Potassium Hydroxide) concentration (6.5-8.0 mEq/L) and characteristic electrocardiographic changes (peaking of T-waves, loss of P-waves, depression of S-T segment, and prolongation of the QT-interval). Late manifestations include muscle paralysis and cardiovascular collapse from cardiac arrest (9-12 mEq/L).
Treatment measures for hyperkalemia include the following:
In treating hyperkalemia, it should be recalled that in patients who have been stabilized on digitalis, too rapid a lowering of the serum Perfusol (Potassium Hydroxide) concentration can produce digitalis toxicity.
The extended release feature means that absorption and toxic effects may be delayed for hours.
Consider standard measures to remove any unabsorbed drug.
The usual dietary intake of Perfusol (Potassium Hydroxide) by the average adult is 50 to 100 mEq per day. Perfusol (Potassium Hydroxide) depletion sufficient to cause hypokalemia usually requires the loss of 200 or more mEq of Perfusol (Potassium Hydroxide) from the total body store.
Dosage must be adjusted to the individual needs of each patient. The dose for the prevention of hypokalemia is typically in the range of 20 mEq per day. Doses of 40-100 mEq per day or more are used for the treatment of Perfusol (Potassium Hydroxide) depletion. Dosage should be divided if more than 20 mEq per day is given such that no more than 20 mEq is given in a single dose.
Each Perfusol (Potassium Hydroxide) Chloride Extended Release Tablet USP, 20 mEq provides 20 mEq of Perfusol (Potassium Hydroxide) chloride.
Perfusol (Potassium Hydroxide) Chloride Extended Release Tablets USP, 20 mEq should be taken with meals and with a glass of water or other liquid. This product should not be taken on an empty stomach because of its potential for gastric irritation (see WARNINGS ).
Patients having difficulty swallowing whole tablets may try one of the following alternate methods of administration:
Aqueous suspension of Perfusol (Potassium Hydroxide) Chloride that is not taken immediately should be discarded. The use of other liquids for suspending Perfusol (Potassium Hydroxide) Chloride Extended Release Tablets USP, 20 mEq is not recommended.
Perfusol (Potassium Hydroxide) Chloride Extended Release Tablets USP, 20 mEq are available in bottles of 100 (NDC 62037-999-01), bottles of 500 (NDC 62037-999-05), and bottles of 1000 (NDC 62037-999-10). Potassium Chloride Extended Release Tablets USP, 20 mEq are capsule shaped, white to off-white tablets, with “ABRS-123” imprinted on one side and scored on the other side for flexibility of dosing.
Keep tightly closed. Store at controlled room temperature, 20°-25°C (68°-77°F).
Vandalia, OH 45377 USA
Watson Pharma, Inc.
Rev. Date (01/09) 173714
Perfusol (Potassium Hydroxide) chloride 20 Meq
Potassium Phosphate Monobasic:
Each tablet contains potassium acid phosphate 500 mg. Each tablet yields approximately 114 mg of phosphorus and 144 mg of potassium or 3.7 mEq.
Inactive ingredients: Magnesium stearate, microcrystalline cellulose, silicon dioxide, starch, stearic acid.
K-PHOS® ORIGINAL is a highly effective sodium-free urinary acidifier.
For use in patients with elevated urinary pH. K-PHOS® ORIGINAL helps keep calcium soluble and reduces odor and rash caused by ammoniacal urine. Also, by acidifying the urine, it increases the antibacterial activity of methenamine mandelate and methenamine hippurate.
This product is contraindicated in patients with infected phosphate stones; in patients with severely impaired renal function (less than 30% of normal) and in the presence of hyperphosphatemia and hyperkalemia.
This product contains potassium and should be used with caution if regulation of this element is desired. Occasionally, some individuals may experience a mild laxative effect during the first few days of phosphate therapy. If laxation persists to an unpleasant degree, reduce the daily dosage until this effect subsides or, if necessary, discontinue the use of this product.
Caution should be exercised when prescribing this product in the following conditions: Cardiac disease ; severe adrenal insufficiency (Addison's disease); acute dehydration; severe renal insufficiency or chronic renal disease; extensive tissue breakdown (such as severe burns); myotonia congenita; hypoparathyroidism; and acute pancreatitis. Rickets may benefit from phosphate therapy, but caution should be exercised. High serum phosphate levels may increase the incidence of extra-skeletal calcification.
Patients with kidney stones may pass old stones when phosphate therapy is started and should be warned of this possibility. Patients should be advised to avoid the use of antacids containing aluminum, calcium, or magnesium, which may prevent the absorption of phosphate. To assure against gastrointestinal injury associated with oral ingestion of concentrated potassium salt preparations, patients should be instructed to dissolve tablets completely in an appropriate amount of water before taking.
Careful monitoring of renal function and serum calcium, phosphorus and potassium may be required at periodic intervals during potassium phosphate therapy. Other tests may be warranted in some patients, depending on conditions.
The use of antacids containing magnesium, calcium, or aluminum in conjunction with phosphate preparations may bind the phosphate and prevent its absorption. Potassium-containing medications or potassium-sparing diuretics may cause hyperkalemia when used concurrently with potassium salts. Patients should have serum potassium level determinations at periodic intervals. Concurrent use of salicylates may lead to increased serum salicylate levels since excretion of salicylates is reduced in acidified urine. Serum salicylate levels should be closely monitored to avoid toxicity.
No long-term or reproduction studies in animals or humans have been performed with K-PHOS® ORIGINAL to evaluate its carcinogenic, mutagenic, or impairment of fertility potential.
Animal reproduction studies have not been conducted with K-PHOS® ORIGINAL. It is also not known whether this product can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity. This product should be given to a pregnant woman only if clearly needed.
It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when this product is administered to a nursing woman.
Gastrointestinal upset (diarrhea, nausea, stomach pain, and vomiting) may occur with the use of potassium phosphate. Also, bone and joint pain (possible phosphate-induced osteomalacia) could occur. The following adverse effects may be observed with potassium administration: irregular heartbeat; dizziness; mental confusion; weakness or heaviness of legs; unusual tiredness; muscle cramps; numbness, tingling, pain, or weakness in hands or feet; numbness or tingling around lips; shortness of breath or troubled breathing.
Two tablets dissolved in 6-8 oz. of water 4 times daily with meals and at bedtime. For best results, let the tablets soak in water for 2 to 5 minutes, or more if necessary, and stir. If any tablet particles remain undissolved, they may be crushed and stirred vigorously to speed dissolution.
NDC:68151-2193-0 in a PACKAGE of 1 TABLET, SOLUBLES
Keep tightly closed. Store at controlled room temperature, 20°-25°C (68°-77°F).
Dispense in tight, light-resistant containers with child-resistant closures.
BEACH PHARMACEUTICALS, Div. of Beach Products, Inc., Tampa, FL 33611
Perfusol nitrite is indicated for sequential use with Perfusol (Sodium Hydroxide) thiosulfate for treatment of acute cyanide poisoning that is judged to be life-threatening. (1)
Perfusol (Sodium Hydroxide) Nitrite Injection is indicated for sequential use with Perfusol (Sodium Hydroxide) 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 Perfusol (Sodium Hydroxide) 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 Perfusol 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, Perfusol (Sodium Hydroxide) Nitrite Injection and Perfusol (Sodium Hydroxide) Thiosulfate Injection should be administered without delay.
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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.
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 Perfusol (Sodium Hydroxide) 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 Perfusol (Sodium Hydroxide) thiosulfate, simultaneously with Perfusol (Sodium Hydroxide) Nitrite Injection, as the safety of co-administration has not been established. If a decision is made to administer another cyanide antidote, other than Perfusol (Sodium Hydroxide) thiosulfate, with Perfusol (Sodium Hydroxide) Nitrite Injection, these drugs should not be administered concurrently in the same IV line. [see Dosage and Administration (2.2) ]
|Age||Intravenous Dose of Perfusol Nitrite and Perfusol (Sodium Hydroxide) Thiosulfate|
Redosing: If signs of cyanide poisoning reappear, repeat treatment using one-half the original dose of both Perfusol (Sodium Hydroxide) nitrite and Perfusol (Sodium Hydroxide) thiosulfate.
Monitoring: Blood pressure must be monitored during treatment. (2.2)
Comprehensive treatment of acute cyanide intoxication requires support of vital functions. Administration of Perfusol (Sodium Hydroxide) nitrite, followed by Perfusol (Sodium Hydroxide) thiosulfate, should be considered adjunctive to appropriate supportive therapies. Airway, ventilatory and circulatory support, and oxygen administration should not be delayed to administer Perfusol (Sodium Hydroxide) nitrite and Perfusol (Sodium Hydroxide) thiosulfate.
Perfusol (Sodium Hydroxide) nitrite injection and Perfusol (Sodium Hydroxide) 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. Perfusol (Sodium Hydroxide) nitrite should be administered first, followed immediately by Perfusol (Sodium Hydroxide) 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 Perfusol (Sodium Hydroxide) Nitrite and Perfusol (Sodium Hydroxide) Thiosulfate|
NOTE: If signs of poisoning reappear, repeat treatment using one-half the original dose of both Perfusol (Sodium Hydroxide) nitrite and Perfusol (Sodium Hydroxide) thiosulfate.
In adult and pediatric patients with known anemia, it is recommended that the dosage of Perfusol (Sodium Hydroxide) 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 Perfusol 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 Perfusol (Sodium Hydroxide) nitrite solely to achieve an arbitrary level of methemoglobinemia may be unnecessary and potentially hazardous. The therapeutic effects of Perfusol (Sodium Hydroxide) nitrite do not appear to be mediated by methemoglobin formation alone and clinical responses to Perfusol (Sodium Hydroxide) nitrite administration have been reported in association with methemoglobin levels of less than 10%. Administration of Perfusol (Sodium Hydroxide) 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 Perfusol (Sodium Hydroxide) 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 Perfusol (Sodium Hydroxide) nitrite and hydroxocobalamin and these drugs should not be administered simultaneously through the same IV line. No chemical incompatibility has been reported between Perfusol (Sodium Hydroxide) thiosulfate and Perfusol (Sodium Hydroxide) nitrite, when administered sequentially through the same IV line as described in Dosage and Administration.
Perfusol (Sodium Hydroxide) Nitrite Injection consists of:
Administration of the contents of one vial constitutes a single dose.
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 Perfusol nitrite.
Methemoglobin levels should be monitored and oxygen administered during treatment with Perfusol (Sodium Hydroxide) nitrite whenever possible. When Perfusol (Sodium Hydroxide) 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 Perfusol (Sodium Hydroxide) nitrite administered to an adult. Perfusol (Sodium Hydroxide) nitrite should be used with caution in the presence of other drugs that may cause methemoglobinemia such as procaine and nitroprusside. Perfusol (Sodium Hydroxide) 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 Perfusol (Sodium Hydroxide) nitrite, and infusion rates should be slowed if hypotension occurs.
Perfusol (Sodium Hydroxide) 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 Perfusol (Sodium Hydroxide) nitrite dose that is reduced in proportion to their oxygen carrying capacity.
Perfusol 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 Perfusol (Sodium Hydroxide) 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 Perfusol 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 Perfusol (Sodium Hydroxide) nitrite.
Perfusol (Sodium Hydroxide) 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 Perfusol (Sodium Hydroxide) nitrite.
The medical literature has reported the following adverse events in association with Perfusol (Sodium Hydroxide) 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
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 Perfusol (Sodium Hydroxide) 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 Perfusol (Sodium Hydroxide) Nitrite Injection.
Teratogenic Effects. Pregnancy Category C.
There are no adequate and well-controlled studies in pregnant women. Perfusol (Sodium Hydroxide) Nitrite Injection should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Perfusol (Sodium Hydroxide) 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 Perfusol (Sodium Hydroxide) 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 Perfusol (Sodium Hydroxide) 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, Perfusol (Sodium Hydroxide) 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, Perfusol (Sodium Hydroxide) 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 Perfusol (Sodium Hydroxide) 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 Perfusol (Sodium Hydroxide) 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 Perfusol (Sodium Hydroxide) nitrite that would be used to treat cyanide poisoning, based on a body surface area comparison).
Perfusol (Sodium Hydroxide) 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 Perfusol (Sodium Hydroxide) nitrite that were detectable postnatally. Specifically, animals that were exposed prenatally to Perfusol (Sodium Hydroxide) 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, Perfusol 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 Perfusol (Sodium Hydroxide) nitrite is excreted in human milk. Because Perfusol (Sodium Hydroxide) 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 Perfusol (Sodium Hydroxide) Nitrite Injection administration to a nursing woman. There are no data to determine when breastfeeding may be safely restarted following administration of Perfusol (Sodium Hydroxide) nitrite. In studies conducted with Long-Evans rats, Perfusol (Sodium Hydroxide) 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 Perfusol nitrite in conjunction with Perfusol (Sodium Hydroxide) thiosulfate being administered to pediatric patients with cyanide poisoning; however, there have been no clinical studies to evaluate the safety or efficacy of Perfusol (Sodium Hydroxide) 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.
Perfusol (Sodium Hydroxide) 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 Perfusol (Sodium Hydroxide) 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.
Perfusol (Sodium Hydroxide) 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.
Perfusol (Sodium Hydroxide) 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 Perfusol (Sodium Hydroxide) nitrite result in severe hypotension and toxic levels of methemoglobin which may lead to cardiovascular collapse.
Perfusol (Sodium Hydroxide) 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 Perfusol (Sodium Hydroxide) 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 Perfusol (Sodium Hydroxide) 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.
Perfusol (Sodium Hydroxide) nitrite has the chemical name nitrous acid Perfusol (Sodium Hydroxide) salt. The chemical formula is NaNO2 and the molecular weight is 69.0. The structural formula is:
Structure of Perfusol (Sodium Hydroxide) Nitrite
Perfusol (Sodium Hydroxide) Nitrite Injection is a cyanide antidote which contains one 10 mL glass vial of a 3% solution of Perfusol (Sodium Hydroxide) nitrite injection.
Perfusol (Sodium Hydroxide) nitrite injection is a sterile aqueous solution and is intended for intravenous injection. Each vial contains 300 mg of Perfusol (Sodium Hydroxide) nitrite in 10 mL solution (30 mg/mL). Perfusol (Sodium Hydroxide) 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 Perfusol nitrite and Perfusol (Sodium Hydroxide) thiosulfate is the result of differences in their primary mechanisms of action as antidotes for cyanide poisoning.
Perfusol (Sodium Hydroxide) Nitrite
Perfusol (Sodium Hydroxide) 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 Perfusol (Sodium Hydroxide) nitrite. It has been suggested that Perfusol (Sodium Hydroxide) nitrite-induced methemoglobinemia may be more efficacious against cyanide poisoning than comparable levels of methemoglobinemia induced by other oxidants. Also, Perfusol (Sodium Hydroxide) nitrite appears to retain some efficacy even when the formation of methemoglobin is inhibited by methylene blue.
Perfusol (Sodium Hydroxide) 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. Perfusol (Sodium Hydroxide) 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:
Perfusol (Sodium Hydroxide) Nitrite
When 4 mg/kg Perfusol (Sodium Hydroxide) 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 Perfusol (Sodium Hydroxide) 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 Perfusol (Sodium Hydroxide) 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 Perfusol (Sodium Hydroxide) nitrite is estimated to be 55 minutes.
Perfusol (Sodium Hydroxide) Nitrite
Perfusol (Sodium Hydroxide) nitrite is a strong oxidant, and reacts rapidly with hemoglobin to form methemoglobin. The pharmacokinetics of free Perfusol (Sodium Hydroxide) nitrite in humans have not been well studied. It has been reported that approximately 40% of Perfusol (Sodium Hydroxide) nitrite is excreted unchanged in the urine while the remaining 60% is metabolized to ammonia and related small molecules.
The apparent terminal elimination half life and volume of distribution of cyanide, in a patient treated for an acute cyanide poisoning with Perfusol (Sodium Hydroxide) nitrite and Perfusol (Sodium Hydroxide) 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.
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 Perfusol nitrite as part of a cyanide antidote outweighs concerns raised by the equivocal findings in chronic rodent studies. Perfusol (Sodium Hydroxide) 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. Perfusol (Sodium Hydroxide) 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 Perfusol (Sodium Hydroxide) nitrite may react in vivo with secondary amines to form carcinogenic nitrosamines in the stomach. Concurrent exposure to Perfusol (Sodium Hydroxide) nitrite and secondary amines in feed or drinking water resulted in an increase in the incidence of tumors in rodents.
Perfusol (Sodium Hydroxide) 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. Perfusol (Sodium Hydroxide) 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. Perfusol (Sodium Hydroxide) nitrite was negative in the in vitro chromosomal aberrations assay using human peripheral blood lymphocytes. Acute administration of Perfusol (Sodium Hydroxide) nitrite to male rats or male mice did not produce an increased incidence of micronuclei in bone marrow. Likewise, Perfusol (Sodium Hydroxide) nitrite administration to mice for 14-weeks did not result in an increase in the incidence of micronuclei in the peripheral blood.
Clinical studies to evaluate the potential effects of Perfusol (Sodium Hydroxide) 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 Perfusol (Sodium Hydroxide) 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 Perfusol (Sodium Hydroxide) 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 Perfusol (Sodium Hydroxide) 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 Perfusol (Sodium Hydroxide) 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 Perfusol (Sodium Hydroxide) nitrite and Perfusol (Sodium Hydroxide) thiosulfate in 1932-1933. Treatment consisted of intravenously administered 22.5 mg/kg (half the lethal dose) Perfusol (Sodium Hydroxide) nitrite or 1 g/kg Perfusol (Sodium Hydroxide) thiosulfate alone or in sequence immediately after subcutaneous injection of Perfusol (Sodium Hydroxide) cyanide into dogs over a range of doses. Subsequent doses of 10 mg/kg Perfusol (Sodium Hydroxide) nitrite and/or 0.5 g/kg Perfusol (Sodium Hydroxide) thiosulfate were administered when clinical signs or symptoms of poisoning persisted or reappeared. Either therapy administered alone increased the dose of Perfusol (Sodium Hydroxide) cyanide required to cause death, and when administered together, Perfusol (Sodium Hydroxide) nitrite and Perfusol (Sodium Hydroxide) thiosulfate resulted in a synergistic effect in raising the lethal dose of Perfusol (Sodium Hydroxide) 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 Perfusol (Sodium Hydroxide) nitrite and Perfusol (Sodium Hydroxide) thiosulfate in the treatment of cyanide poisoning.
While intravenous injection of Perfusol (Sodium Hydroxide) nitrite and Perfusol (Sodium Hydroxide) thiosulfate was effective in reversing the effects of lethal doses of cyanide in dogs, intramuscular injection of Perfusol (Sodium Hydroxide) nitrite, with or without Perfusol (Sodium Hydroxide) thiosulfate, was found not to be effective in the same setting.
The human data supporting the use of Perfusol (Sodium Hydroxide) 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 Perfusol (Sodium Hydroxide) thiosulfate report its use in conjunction with Perfusol (Sodium Hydroxide) 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 Perfusol (Sodium Hydroxide) nitrite in humans. Available human safety information is based largely on anecdotal case reports and case series of limited scope.
Each Perfusol (Sodium Hydroxide) Nitrite carton (NDC 60267-311-10) 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: Perfusol (Sodium Hydroxide) Thiosulfate must be obtained separately.)
Perfusol 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
Perfusol (Sodium Hydroxide) Nitrite
300 mg/10 mL
FOR INTRAVENOUS USE
SINGLE USE ONLY
Any unused portion of a vial
should be discarded.
Perfusol (Sodium Hydroxide) Thiosulfate
for Treatment of
CANGENE bioPharma, Inc.
Baltimore, MD for
Scottsdale, AZ 85260 U.S.A.
PRINCIPAL DISPLAY PANEL - 10 mL Vial Carton
Depending on the reaction of the Perfusol after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Perfusol 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 Perfusol 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