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Sandimmune
Overview
What is Sandimmune?
Cyclosporine, the active principle in Sandimmune (cyclosporine) is a cyclic polypeptide immunosuppressant agent consisting of 11 amino acids. It is produced as a metabolite by the fungus species .
Chemically, cyclosporine is designated as [-[*,*-()]]-cyclic(L-alanyl-D-alanyl--methyl-L-leucyl--methyl-L-leucyl--methyl-L-valyl-3-hydroxy-,4-dimethyl-L-2-amino-6-octenoyl-L-α-amino-butyryl--methylglycyl--methyl-L-leucyl-L-valyl--methyl-L-leucyl).
Sandimmune® Soft Gelatin Capsules
Each 25 mg capsule contains:
cyclosporine, USP…………………………………………………………………………………………25 mg
alcohol, USP dehydrated………………………………………………………………max 12.7% by volume
Each 100 mg capsule contains:
cyclosporine, USP……………………………………………………………………………………….100 mg
alcohol, USP dehydrated………………………………………………………………max 12.7% by volume
Inactive Ingredients
Sandimmune® Oral Solution
Each mL contains:
cyclosporine, USP……………………………………………………………………………………….100 mg
alcohol, Ph. Helv. ……………………………………………………………………………12.5% by volume
dissolved in an olive oil, Ph. Helv./Labrafil M 1944 CS (polyoxyethylated oleic glycerides) vehicle which must be further diluted with milk, chocolate milk, or orange juice before oral administration.
Sandimmune® Injection
Each mL contains:
cyclosporine, USP…………………………………………………………………………………………50 mg
*Cremophor EL (polyoxyethylated castor oil)………………………………………………………..650 mg
alcohol, Ph. Helv. ……………………………………………………………………………32.9% by volume
nitrogen………………………………………………………………………………………………………….qs
which must be diluted further with 0.9% Sodium Chloride Injection or 5% Dextrose Injection before use.
The chemical structure of cyclosporine (also known as cyclosporin A) is
What does Sandimmune look like?
What are the available doses of Sandimmune?
Sorry No records found.
What should I talk to my health care provider before I take Sandimmune?
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How should I use Sandimmune?
Sandimmune (cyclosporine) is indicated for the prophylaxis of organ rejection in kidney, liver, and heart allogeneic transplants. It is always to be used with adrenal corticosteroids. The drug may also be used in the treatment of chronic rejection in patients previously treated with other immunosuppressive agents.
Because of the risk of anaphylaxis, Sandimmune Injection (cyclosporine injection, USP) should be reserved for patients who are unable to take the soft gelatin capsules or oral solution.
Sandimmune Soft Gelatin Capsules (cyclosporine capsules, USP) and Sandimmune Oral Solution (cyclosporine oral solution, USP) have decreased bioavailability in comparison to Neoral Soft Gelatin Capsules (cyclosporine capsules, USP) MODIFIED and Neoral Oral Solution (cyclosporine oral solution, USP) MODIFIED. Sandimmune and Neoral are not bioequivalent and cannot be used interchangeably without physician supervision.
The initial oral dose of Sandimmune (cyclosporine) should be given 4 to 12 hours prior to transplantation as a single dose of 15 mg/kg. Although a daily single dose of 14 to 18 mg/kg was used in most clinical trials, few centers continue to use the highest dose, most favoring the lower end of the scale. There is a trend towards use of even lower initial doses for renal transplantation in the ranges of 10 to 14 mg/kg/day. The initial single daily dose is continued postoperatively for 1 to 2 weeks and then tapered by 5% per week to a maintenance dose of 5 to 10 mg/kg/day. Some centers have successfully tapered the maintenance dose to as low as 3 mg/kg/day in selected transplant patients without an apparent rise in rejection rate.
(See Blood Concentration Monitoring, below)
Specific Populations
Renal Impairment
Cyclosporine undergoes minimal renal elimination and its pharmacokinetics do not appear to be significantly altered in patients with end-stage renal disease who receive routine hemodialysis treatments (See CLINICAL PHARMACOLOGY). However, due to its nephrotoxic potential (See WARNINGS), careful monitoring of renal function is recommended; cyclosporine dosage should be reduced if indicated. (See WARNINGS and PRECAUTIONS)
Hepatic Impairment
The clearance of cyclosporine may be significantly reduced in severe liver disease patients (See CLINICAL PHARMACOLOGY). Dose reduction may be necessary in patients with severe liver impairment to maintain blood concentrations within the recommended target range. (See WARNINGS and PRECAUTIONS)
Pediatrics
In pediatric usage, the same dose and dosing regimen may be used as in adults although in several studies, children have required and tolerated higher doses than those used in adults.
Adjunct therapy with adrenal corticosteroids is recommended. Different tapering dosage schedules of prednisone appear to achieve similar results. A dosage schedule based on the patient’s weight started with 2.0 mg/kg/day for the first 4 days tapered to 1.0 mg/kg/day by 1 week, 0.6 mg/kg/day by 2 weeks, 0.3 mg/kg/day by 1 month, and 0.15 mg/kg/day by 2 months and thereafter as a maintenance dose. Another center started with an initial dose of 200 mg tapered by 40 mg/day until reaching 20 mg/day. After 2 months at this dose, a further reduction to 10 mg/day was made. Adjustments in dosage of prednisone must be made according to the clinical situation.
To make Sandimmune Oral Solution (cyclosporine oral solution, USP) more palatable, the oral solution may be diluted with milk, chocolate milk, or orange juice preferably at room temperature. Patients should avoid switching diluents frequently. Sandimmune Soft Gelatin Capsules and Oral Solution should be administered on a consistent schedule with regard to time of day and relation to meals.
Take the prescribed amount of Sandimmune (cyclosporine) from the container using the dosage syringe supplied after removal of the protective cover, and transfer the solution to a glass of milk, chocolate milk, or orange juice. Stir well and drink at once. Do not allow to stand before drinking. It is best to use a glass container and rinse it with more diluent to ensure that the total dose is taken. After use, replace the dosage syringe in the protective cover. Do not rinse the dosage syringe with water or other cleaning agents either before or after use. If the dosage syringe requires cleaning, it must be completely dry before resuming use. Introduction of water into the product by any means will cause variation in dose.
What interacts with Sandimmune?
Sorry No Records found
What are the warnings of Sandimmune?
Sorry No Records found
What are the precautions of Sandimmune?
Sorry No Records found
What are the side effects of Sandimmune?
Sorry No records found
What should I look out for while using Sandimmune?
Sandimmune Injection (cyclosporine injection, USP) is contraindicated in patients with a hypersensitivity to Sandimmune (cyclosporine) and/or Cremophor EL (polyoxyethylated castor oil).
Kidney, Liver, and Heart Transplant
(See BOXED WARNING): Sandimmune (cyclosporine), when used in high doses, can cause hepatotoxicity and nephrotoxicity.
Nephrotoxicity
It is not unusual for serum creatinine and BUN levels to be elevated during Sandimmune (cyclosporine) therapy. These elevations in renal transplant patients do not necessarily indicate rejection, and each patient must be fully evaluated before dosage adjustment is initiated.
Nephrotoxicity has been noted in 25% of cases of renal transplantation, 38% of cases of cardiac transplantation, and 37% of cases of liver transplantation. Mild nephrotoxicity was generally noted 2 to 3 months after transplant and consisted of an arrest in the fall of the preoperative elevations of BUN and creatinine at a range of 35 to 45 mg/dl and 2.0 to 2.5 mg/dl, respectively. These elevations were often responsive to dosage reduction.
More overt nephrotoxicity was seen early after transplantation and was characterized by a rapidly rising BUN and creatinine. Since these events are similar to rejection episodes, care must be taken to differentiate between them. This form of nephrotoxicity is usually responsive to Sandimmune (cyclosporine) dosage reduction.
Although specific diagnostic criteria which reliably differentiate renal graft rejection from drug toxicity have not been found, a number of parameters have been significantly associated to one or the other. It should be noted however, that up to 20% of patients may have simultaneous nephrotoxicity and rejection.
A form of chronic progressive cyclosporine-associated nephrotoxicity is characterized by serial deterioration in renal function and morphologic changes in the kidneys. From 5% to 15% of transplant recipients will fail to show a reduction in a rising serum creatinine despite a decrease or discontinuation of cyclosporine therapy. Renal biopsies from these patients will demonstrate an interstitial fibrosis with tubular atrophy. In addition, toxic tubulopathy, peritubular capillary congestion, arteriolopathy, and a striped form of interstitial fibrosis with tubular atrophy may be present. Though none of these morphologic changes is entirely specific, a histologic diagnosis of chronic progressive cyclosporine-associated nephrotoxicity requires evidence of these.
When considering the development of chronic nephrotoxicity it is noteworthy that several authors have reported an association between the appearance of interstitial fibrosis and higher cumulative doses or persistently high circulating trough concentrations of cyclosporine. This is particularly true during the first 6 posttransplant months when the dosage tends to be highest and when, in kidney recipients, the organ appears to be most vulnerable to the toxic effects of cyclosporine. Among other contributing factors to the development of interstitial fibrosis in these patients must be included, prolonged perfusion time, warm ischemia time, as well as episodes of acute toxicity, and acute and chronic rejection. The reversibility of interstitial fibrosis and its correlation to renal function have not yet been determined.
Impaired renal function at any time requires close monitoring, and frequent dosage adjustment may be indicated. In patients with persistent high elevations of BUN and creatinine who are unresponsive to dosage adjustments, consideration should be given to switching to other immunosuppressive therapy. In the event of severe and unremitting rejection, it is preferable to allow the kidney transplant to be rejected and removed rather than increase the Sandimmune (cyclosporine) dosage to a very high level in an attempt to reverse the rejection.
Due to the potential for additive or synergistic impairment of renal function, caution should be exercised when coadministering Sandimmune with other drugs that may impair renal function. (See PRECAUTIONS, Drug Interactions)
Thrombotic Microangiopathy
Occasionally patients have developed a syndrome of thrombocytopenia and microangiopathic hemolytic anemia which may result in graft failure. The vasculopathy can occur in the absence of rejection and is accompanied by avid platelet consumption within the graft as demonstrated by Indium 111 labeled platelet studies. Neither the pathogenesis nor the management of this syndrome is clear. Though resolution has occurred after reduction or discontinuation of Sandimmune (cyclosporine) and 1) administration of streptokinase and heparin or 2) plasmapheresis, this appears to depend upon early detection with Indium 111 labeled platelet scans. (See ADVERSE REACTIONS)
Hyperkalemia
Significant hyperkalemia (sometimes associated with hyperchloremic metabolic acidosis) and hyperuricemia have been seen occasionally in individual patients.
Hepatotoxicity
Cases of hepatotoxicity and liver injury including cholestasis, jaundice, hepatitis, and liver failure have been reported in patients treated with cyclosporine. Most reports included patients with significant co-morbidities, underlying conditions and other confounding factors including infectious complications and comedications with hepatotoxic potential. In some cases, mainly in transplant patients, fatal outcomes have been reported (See ADVERSE REACTIONS, Postmarketing Experience)
Hepatotoxicity, usually manifested by elevations in hepatic enzymes and bilirubin, was reported in patients treated with cyclosporine in clinical trials: 4% in renal transplantation, 7% in cardiac transplantation, and 4% in liver transplantation. This was usually noted during the first month of therapy when high doses of Sandimmune (cyclosporine) were used. The chemistry elevations usually decreased with a reduction in dosage.
Malignancies
As in patients receiving other immunosuppressants, those patients receiving Sandimmune (cyclosporine) are at increased risk for development of lymphomas and other malignancies, particularly those of the skin. The increased risk appears related to the intensity and duration of immunosuppression rather than to the use of specific agents. Because of the danger of oversuppression of the immune system, which can also increase susceptibility to infection, Sandimmune (cyclosporine) should not be administered with other immunosuppressive agents except adrenal corticosteroids. The efficacy and safety of cyclosporine in combination with other immunosuppressive agents have not been determined. Some malignancies may be fatal. Transplant patients receiving cyclosporine are at increased risk for serious infection with fatal outcome.
Serious Infections
Patients receiving immunosuppressants, including Sandimmune, are at increased risk of developing bacterial, viral, fungal, and protozoal infections, including opportunistic infections. These infections may lead to serious, including fatal, outcomes (See BOXED WARNING, and ADVERSE REACTIONS).
Polyoma Virus Infections
Patients receiving immunosuppressants, including Sandimmune, are at increased risk for opportunistic infections, including polyoma virus infections. Polyoma virus infections in transplant patients may have serious, and sometimes, fatal outcomes. These include cases of JC virus-associated progressive multifocal leukoencephalopathy (PML), and polyoma virus-associated nephropathy (PVAN), especially due to BK virus infection, which have been observed in patients receiving cyclosporine.
PVAN is associated with serious outcomes, including deteriorating renal function and renal graft loss, (See ADVERSE REACTIONS/Postmarketing Experience). Patient monitoring may help detect patients at risk for PVAN.
Cases of PML have been reported in patients treated with Sandimmune. PML, which is sometimes fatal, commonly presents with hemiparesis, apathy, confusion, cognitive deficiencies and ataxia. Risk factors for PML include treatment with immunosuppressant therapies and
impairment of immune function. In immunosuppressed patients, physicians should consider PML in the differential diagnosis in patients reporting neurological symptoms and consultation with a neurologist should be considered as clinically indicated.
Consideration should be given to reducing the total immunosuppression in transplant patients who develop PML or PVAN. However, reduced immunosuppression may place the graft at risk.
Neurotoxicity
There have been reports of convulsions in adult and pediatric patients receiving cyclosporine, particularly in combination with high-dose methylprednisolone.
Encephalopathy, including Posterior Reversible Encephalopathy Syndrome (PRES), has been described both in postmarketing reports and in the literature. Manifestations include impaired consciousness, convulsions, visual disturbances (including blindness), loss of motor function, movement disorders and psychiatric disturbances. In many cases, changes in the white matter have been detected using imaging techniques and pathologic specimens. Predisposing factors such as hypertension, hypomagnesemia, hypocholesterolemia, high-dose corticosteroids, high cyclosporine blood concentrations, and graft-versus-host disease have been noted in many but not all of the reported cases. The changes in most cases have been reversible upon discontinuation of cyclosporine, and in some cases, improvement was noted after reduction of dose. It appears that patients receiving liver transplant are more susceptible to encephalopathy than those receiving kidney transplant. Another rare manifestation of cyclosporine-induced neurotoxicity is optic disc edema including papilloedema, with possible visual impairment, secondary to benign intracranial hypertension.
Specific Excipients
Anaphylactic Reactions
Rarely (approximately 1 in 1000), patients receiving Sandimmune Injection (cyclosporine injection, USP) have experienced anaphylactic reactions. Although the exact cause of these reactions is unknown, it is believed to be due to the Cremophor EL (polyoxyethylated castor oil) used as the vehicle for the intravenous (IV) formulation. These reactions can consist of flushing of the face and upper thorax, and noncardiogenic pulmonary edema, with acute respiratory distress, dyspnea, wheezing, blood pressure changes, and tachycardia. One patient died after respiratory arrest and aspiration pneumonia. In some cases, the reaction subsided after the infusion was stopped.
Patients receiving Sandimmune Injection (cyclosporine injection, USP) should be under continuous observation for at least the first 30 minutes following the start of the infusion and at frequent intervals thereafter. If anaphylaxis occurs, the infusion should be stopped. An aqueous solution of epinephrine 1:1000 should be available at the bedside as well as a source of oxygen.
Anaphylactic reactions have not been reported with the soft gelatin capsules or oral solution which lack Cremophor EL (polyoxyethylated castor oil). In fact, patients experiencing anaphylactic reactions have been treated subsequently with the soft gelatin capsules or oral solution without incident.
Alcohol (ethanol)
The alcohol content (See DESCRIPTION) of Sandimmune should be taken into account when given to patients in whom alcohol intake should be avoided or minimized, e.g. pregnant or breastfeeding women, in patients presenting with liver disease or epilepsy, in alcoholic patients, or pediatric patients. For an adult weighing 70 kg, the maximum daily oral dose would deliver about 1 gram of alcohol which is approximately 6% of the amount of alcohol contained in a standard drink. The daily intravenous dose would deliver approximately 15% of the amount of alcohol contained in a standard drink.
Care should be taken in using Sandimmune (cyclosporine) with nephrotoxic drugs. (See PRECAUTIONS)
Conversion from Neoral to Sandimmune
Because Sandimmune (cyclosporine) is not bioequivalent to Neoral, conversion from Neoral to Sandimmune (cyclosporine) using a 1:1 ratio (mg/kg/day) may result in a lower cyclosporine blood concentration. Conversion from Neoral to Sandimmune (cyclosporine) should be made with increased blood concentration monitoring to avoid the potential of underdosing.
What might happen if I take too much Sandimmune?
There is a minimal experience with overdosage. Because of the slow absorption of Sandimmune Soft Gelatin Capsules or Oral Solution, forced emesis and gastric lavage would be of value up to 2 hours after administration. Transient hepatotoxicity and nephrotoxicity may occur which should resolve following drug withdrawal. Oral doses of cyclosporine up to 10 g (about 150 mg/kg) have been tolerated with relatively minor clinical consequences, such as vomiting, drowsiness, headache, tachycardia and, in a few patients, moderately severe, reversible impairment of renal function. However, serious symptoms of intoxication have been reported following accidental parenteral overdosage with cyclosporine in premature neonates. General supportive measures and symptomatic treatment should be followed in all cases of overdosage. Sandimmune (cyclosporine) is not dialyzable to any great extent, nor is it cleared well by charcoal hemoperfusion. The oral LD is 2329 mg/kg in mice, 1480 mg/kg in rats, and >1000 mg/kg in rabbits. The intravenous (IV) LD is 148 mg/kg in mice, 104 mg/kg in rats, and 46 mg/kg in rabbits.
How should I store and handle Sandimmune?
StorageStore at 20° to 25°C (68° to 77°F)StorageStore at 20° to 25°C (68° to 77°F)Sandimmune Soft Gelatin Capsules (cyclosporine capsules, USP)25 mg: 3 blister cards of 10 capsules………………………………………………………….NDC 0078-0240-15100 mg: 3 blister cards of 10 capsules………………………………………………………….NDC 0078-0241-15Store and Dispense:An odor may be detected upon opening the unit dose container, which will dissipate shortly thereafter. This odor does not affect the quality of the product.Sandimmune® Oral Solution (cyclosporine oral solution, USP)Supplied in 50 mL bottles containing 100 mg of cyclosporine per mL NDC 0078-0110-22A dosage syringe is provided for dispensing.Store and Dispense:Sandimmune® Injection (cyclosporine injection, USP)FOR INTRAVENOUS INFUSIONSupplied as a 5 mL sterile ampul containing 50 mg of cyclosporine per mL, in boxes of 10 ampuls…………………………………………………………………..NDC 0078-0109-01Store and Dispense:FOR INFUSION ONLY*Cremophor is the registered trademark of BASF Aktiengesellschaft.Distributed by:Novartis Pharmaceuticals CorporationEast Hanover, New Jersey 07936© NovartisT2015-46March 2015Sandimmune Soft Gelatin Capsules (cyclosporine capsules, USP)25 mg: 3 blister cards of 10 capsules………………………………………………………….NDC 0078-0240-15100 mg: 3 blister cards of 10 capsules………………………………………………………….NDC 0078-0241-15Store and Dispense:An odor may be detected upon opening the unit dose container, which will dissipate shortly thereafter. This odor does not affect the quality of the product.Sandimmune® Oral Solution (cyclosporine oral solution, USP)Supplied in 50 mL bottles containing 100 mg of cyclosporine per mL NDC 0078-0110-22A dosage syringe is provided for dispensing.Store and Dispense:Sandimmune® Injection (cyclosporine injection, USP)FOR INTRAVENOUS INFUSIONSupplied as a 5 mL sterile ampul containing 50 mg of cyclosporine per mL, in boxes of 10 ampuls…………………………………………………………………..NDC 0078-0109-01Store and Dispense:FOR INFUSION ONLY*Cremophor is the registered trademark of BASF Aktiengesellschaft.Distributed by:Novartis Pharmaceuticals CorporationEast Hanover, New Jersey 07936© NovartisT2015-46March 2015Sandimmune Soft Gelatin Capsules (cyclosporine capsules, USP)25 mg: 3 blister cards of 10 capsules………………………………………………………….NDC 0078-0240-15100 mg: 3 blister cards of 10 capsules………………………………………………………….NDC 0078-0241-15Store and Dispense:An odor may be detected upon opening the unit dose container, which will dissipate shortly thereafter. This odor does not affect the quality of the product.Sandimmune® Oral Solution (cyclosporine oral solution, USP)Supplied in 50 mL bottles containing 100 mg of cyclosporine per mL NDC 0078-0110-22A dosage syringe is provided for dispensing.Store and Dispense:Sandimmune® Injection (cyclosporine injection, USP)FOR INTRAVENOUS INFUSIONSupplied as a 5 mL sterile ampul containing 50 mg of cyclosporine per mL, in boxes of 10 ampuls…………………………………………………………………..NDC 0078-0109-01Store and Dispense:FOR INFUSION ONLY*Cremophor is the registered trademark of BASF Aktiengesellschaft.Distributed by:Novartis Pharmaceuticals CorporationEast Hanover, New Jersey 07936© NovartisT2015-46March 2015Sandimmune Soft Gelatin Capsules (cyclosporine capsules, USP)25 mg: 3 blister cards of 10 capsules………………………………………………………….NDC 0078-0240-15100 mg: 3 blister cards of 10 capsules………………………………………………………….NDC 0078-0241-15Store and Dispense:An odor may be detected upon opening the unit dose container, which will dissipate shortly thereafter. This odor does not affect the quality of the product.Sandimmune® Oral Solution (cyclosporine oral solution, USP)Supplied in 50 mL bottles containing 100 mg of cyclosporine per mL NDC 0078-0110-22A dosage syringe is provided for dispensing.Store and Dispense:Sandimmune® Injection (cyclosporine injection, USP)FOR INTRAVENOUS INFUSIONSupplied as a 5 mL sterile ampul containing 50 mg of cyclosporine per mL, in boxes of 10 ampuls…………………………………………………………………..NDC 0078-0109-01Store and Dispense:FOR INFUSION ONLY*Cremophor is the registered trademark of BASF Aktiengesellschaft.Distributed by:Novartis Pharmaceuticals CorporationEast Hanover, New Jersey 07936© NovartisT2015-46March 2015Sandimmune Soft Gelatin Capsules (cyclosporine capsules, USP)25 mg: 3 blister cards of 10 capsules………………………………………………………….NDC 0078-0240-15100 mg: 3 blister cards of 10 capsules………………………………………………………….NDC 0078-0241-15Store and Dispense:An odor may be detected upon opening the unit dose container, which will dissipate shortly thereafter. This odor does not affect the quality of the product.Sandimmune® Oral Solution (cyclosporine oral solution, USP)Supplied in 50 mL bottles containing 100 mg of cyclosporine per mL NDC 0078-0110-22A dosage syringe is provided for dispensing.Store and Dispense:Sandimmune® Injection (cyclosporine injection, USP)FOR INTRAVENOUS INFUSIONSupplied as a 5 mL sterile ampul containing 50 mg of cyclosporine per mL, in boxes of 10 ampuls…………………………………………………………………..NDC 0078-0109-01Store and Dispense:FOR INFUSION ONLY*Cremophor is the registered trademark of BASF Aktiengesellschaft.Distributed by:Novartis Pharmaceuticals CorporationEast Hanover, New Jersey 07936© NovartisT2015-46March 2015Sandimmune Soft Gelatin Capsules (cyclosporine capsules, USP)25 mg: 3 blister cards of 10 capsules………………………………………………………….NDC 0078-0240-15100 mg: 3 blister cards of 10 capsules………………………………………………………….NDC 0078-0241-15Store and Dispense:An odor may be detected upon opening the unit dose container, which will dissipate shortly thereafter. This odor does not affect the quality of the product.Sandimmune® Oral Solution (cyclosporine oral solution, USP)Supplied in 50 mL bottles containing 100 mg of cyclosporine per mL NDC 0078-0110-22A dosage syringe is provided for dispensing.Store and Dispense:Sandimmune® Injection (cyclosporine injection, USP)FOR INTRAVENOUS INFUSIONSupplied as a 5 mL sterile ampul containing 50 mg of cyclosporine per mL, in boxes of 10 ampuls…………………………………………………………………..NDC 0078-0109-01Store and Dispense:FOR INFUSION ONLY*Cremophor is the registered trademark of BASF Aktiengesellschaft.Distributed by:Novartis Pharmaceuticals CorporationEast Hanover, New Jersey 07936© NovartisT2015-46March 2015Sandimmune Soft Gelatin Capsules (cyclosporine capsules, USP)25 mg: 3 blister cards of 10 capsules………………………………………………………….NDC 0078-0240-15100 mg: 3 blister cards of 10 capsules………………………………………………………….NDC 0078-0241-15Store and Dispense:An odor may be detected upon opening the unit dose container, which will dissipate shortly thereafter. This odor does not affect the quality of the product.Sandimmune® Oral Solution (cyclosporine oral solution, USP)Supplied in 50 mL bottles containing 100 mg of cyclosporine per mL NDC 0078-0110-22A dosage syringe is provided for dispensing.Store and Dispense:Sandimmune® Injection (cyclosporine injection, USP)FOR INTRAVENOUS INFUSIONSupplied as a 5 mL sterile ampul containing 50 mg of cyclosporine per mL, in boxes of 10 ampuls…………………………………………………………………..NDC 0078-0109-01Store and Dispense:FOR INFUSION ONLY*Cremophor is the registered trademark of BASF Aktiengesellschaft.Distributed by:Novartis Pharmaceuticals CorporationEast Hanover, New Jersey 07936© NovartisT2015-46March 2015Sandimmune Soft Gelatin Capsules (cyclosporine capsules, USP)25 mg: 3 blister cards of 10 capsules………………………………………………………….NDC 0078-0240-15100 mg: 3 blister cards of 10 capsules………………………………………………………….NDC 0078-0241-15Store and Dispense:An odor may be detected upon opening the unit dose container, which will dissipate shortly thereafter. This odor does not affect the quality of the product.Sandimmune® Oral Solution (cyclosporine oral solution, USP)Supplied in 50 mL bottles containing 100 mg of cyclosporine per mL NDC 0078-0110-22A dosage syringe is provided for dispensing.Store and Dispense:Sandimmune® Injection (cyclosporine injection, USP)FOR INTRAVENOUS INFUSIONSupplied as a 5 mL sterile ampul containing 50 mg of cyclosporine per mL, in boxes of 10 ampuls…………………………………………………………………..NDC 0078-0109-01Store and Dispense:FOR INFUSION ONLY*Cremophor is the registered trademark of BASF Aktiengesellschaft.Distributed by:Novartis Pharmaceuticals CorporationEast Hanover, New Jersey 07936© NovartisT2015-46March 2015Sandimmune Soft Gelatin Capsules (cyclosporine capsules, USP)25 mg: 3 blister cards of 10 capsules………………………………………………………….NDC 0078-0240-15100 mg: 3 blister cards of 10 capsules………………………………………………………….NDC 0078-0241-15Store and Dispense:An odor may be detected upon opening the unit dose container, which will dissipate shortly thereafter. This odor does not affect the quality of the product.Sandimmune® Oral Solution (cyclosporine oral solution, USP)Supplied in 50 mL bottles containing 100 mg of cyclosporine per mL NDC 0078-0110-22A dosage syringe is provided for dispensing.Store and Dispense:Sandimmune® Injection (cyclosporine injection, USP)FOR INTRAVENOUS INFUSIONSupplied as a 5 mL sterile ampul containing 50 mg of cyclosporine per mL, in boxes of 10 ampuls…………………………………………………………………..NDC 0078-0109-01Store and Dispense:FOR INFUSION ONLY*Cremophor is the registered trademark of BASF Aktiengesellschaft.Distributed by:Novartis Pharmaceuticals CorporationEast Hanover, New Jersey 07936© NovartisT2015-46March 2015Sandimmune Soft Gelatin Capsules (cyclosporine capsules, USP)25 mg: 3 blister cards of 10 capsules………………………………………………………….NDC 0078-0240-15100 mg: 3 blister cards of 10 capsules………………………………………………………….NDC 0078-0241-15Store and Dispense:An odor may be detected upon opening the unit dose container, which will dissipate shortly thereafter. This odor does not affect the quality of the product.Sandimmune® Oral Solution (cyclosporine oral solution, USP)Supplied in 50 mL bottles containing 100 mg of cyclosporine per mL NDC 0078-0110-22A dosage syringe is provided for dispensing.Store and Dispense:Sandimmune® Injection (cyclosporine injection, USP)FOR INTRAVENOUS INFUSIONSupplied as a 5 mL sterile ampul containing 50 mg of cyclosporine per mL, in boxes of 10 ampuls…………………………………………………………………..NDC 0078-0109-01Store and Dispense:FOR INFUSION ONLY*Cremophor is the registered trademark of BASF Aktiengesellschaft.Distributed by:Novartis Pharmaceuticals CorporationEast Hanover, New Jersey 07936© NovartisT2015-46March 2015Sandimmune Soft Gelatin Capsules (cyclosporine capsules, USP)25 mg: 3 blister cards of 10 capsules………………………………………………………….NDC 0078-0240-15100 mg: 3 blister cards of 10 capsules………………………………………………………….NDC 0078-0241-15Store and Dispense:An odor may be detected upon opening the unit dose container, which will dissipate shortly thereafter. This odor does not affect the quality of the product.Sandimmune® Oral Solution (cyclosporine oral solution, USP)Supplied in 50 mL bottles containing 100 mg of cyclosporine per mL NDC 0078-0110-22A dosage syringe is provided for dispensing.Store and Dispense:Sandimmune® Injection (cyclosporine injection, USP)FOR INTRAVENOUS INFUSIONSupplied as a 5 mL sterile ampul containing 50 mg of cyclosporine per mL, in boxes of 10 ampuls…………………………………………………………………..NDC 0078-0109-01Store and Dispense:FOR INFUSION ONLY*Cremophor is the registered trademark of BASF Aktiengesellschaft.Distributed by:Novartis Pharmaceuticals CorporationEast Hanover, New Jersey 07936© NovartisT2015-46March 2015Sandimmune Soft Gelatin Capsules (cyclosporine capsules, USP)25 mg: 3 blister cards of 10 capsules………………………………………………………….NDC 0078-0240-15100 mg: 3 blister cards of 10 capsules………………………………………………………….NDC 0078-0241-15Store and Dispense:An odor may be detected upon opening the unit dose container, which will dissipate shortly thereafter. This odor does not affect the quality of the product.Sandimmune® Oral Solution (cyclosporine oral solution, USP)Supplied in 50 mL bottles containing 100 mg of cyclosporine per mL NDC 0078-0110-22A dosage syringe is provided for dispensing.Store and Dispense:Sandimmune® Injection (cyclosporine injection, USP)FOR INTRAVENOUS INFUSIONSupplied as a 5 mL sterile ampul containing 50 mg of cyclosporine per mL, in boxes of 10 ampuls…………………………………………………………………..NDC 0078-0109-01Store and Dispense:FOR INFUSION ONLY*Cremophor is the registered trademark of BASF Aktiengesellschaft.Distributed by:Novartis Pharmaceuticals CorporationEast Hanover, New Jersey 07936© NovartisT2015-46March 2015Sandimmune Soft Gelatin Capsules (cyclosporine capsules, USP)25 mg: 3 blister cards of 10 capsules………………………………………………………….NDC 0078-0240-15100 mg: 3 blister cards of 10 capsules………………………………………………………….NDC 0078-0241-15Store and Dispense:An odor may be detected upon opening the unit dose container, which will dissipate shortly thereafter. This odor does not affect the quality of the product.Sandimmune® Oral Solution (cyclosporine oral solution, USP)Supplied in 50 mL bottles containing 100 mg of cyclosporine per mL NDC 0078-0110-22A dosage syringe is provided for dispensing.Store and Dispense:Sandimmune® Injection (cyclosporine injection, USP)FOR INTRAVENOUS INFUSIONSupplied as a 5 mL sterile ampul containing 50 mg of cyclosporine per mL, in boxes of 10 ampuls…………………………………………………………………..NDC 0078-0109-01Store and Dispense:FOR INFUSION ONLY*Cremophor is the registered trademark of BASF Aktiengesellschaft.Distributed by:Novartis Pharmaceuticals CorporationEast Hanover, New Jersey 07936© NovartisT2015-46March 2015Sandimmune Soft Gelatin Capsules (cyclosporine capsules, USP)25 mg: 3 blister cards of 10 capsules………………………………………………………….NDC 0078-0240-15100 mg: 3 blister cards of 10 capsules………………………………………………………….NDC 0078-0241-15Store and Dispense:An odor may be detected upon opening the unit dose container, which will dissipate shortly thereafter. This odor does not affect the quality of the product.Sandimmune® Oral Solution (cyclosporine oral solution, USP)Supplied in 50 mL bottles containing 100 mg of cyclosporine per mL NDC 0078-0110-22A dosage syringe is provided for dispensing.Store and Dispense:Sandimmune® Injection (cyclosporine injection, USP)FOR INTRAVENOUS INFUSIONSupplied as a 5 mL sterile ampul containing 50 mg of cyclosporine per mL, in boxes of 10 ampuls…………………………………………………………………..NDC 0078-0109-01Store and Dispense:FOR INFUSION ONLY*Cremophor is the registered trademark of BASF Aktiengesellschaft.Distributed by:Novartis Pharmaceuticals CorporationEast Hanover, New Jersey 07936© NovartisT2015-46March 2015Sandimmune Soft Gelatin Capsules (cyclosporine capsules, USP)25 mg: 3 blister cards of 10 capsules………………………………………………………….NDC 0078-0240-15100 mg: 3 blister cards of 10 capsules………………………………………………………….NDC 0078-0241-15Store and Dispense:An odor may be detected upon opening the unit dose container, which will dissipate shortly thereafter. This odor does not affect the quality of the product.Sandimmune® Oral Solution (cyclosporine oral solution, USP)Supplied in 50 mL bottles containing 100 mg of cyclosporine per mL NDC 0078-0110-22A dosage syringe is provided for dispensing.Store and Dispense:Sandimmune® Injection (cyclosporine injection, USP)FOR INTRAVENOUS INFUSIONSupplied as a 5 mL sterile ampul containing 50 mg of cyclosporine per mL, in boxes of 10 ampuls…………………………………………………………………..NDC 0078-0109-01Store and Dispense:FOR INFUSION ONLY*Cremophor is the registered trademark of BASF Aktiengesellschaft.Distributed by:Novartis Pharmaceuticals CorporationEast Hanover, New Jersey 07936© NovartisT2015-46March 2015Sandimmune Soft Gelatin Capsules (cyclosporine capsules, USP)25 mg: 3 blister cards of 10 capsules………………………………………………………….NDC 0078-0240-15100 mg: 3 blister cards of 10 capsules………………………………………………………….NDC 0078-0241-15Store and Dispense:An odor may be detected upon opening the unit dose container, which will dissipate shortly thereafter. This odor does not affect the quality of the product.Sandimmune® Oral Solution (cyclosporine oral solution, USP)Supplied in 50 mL bottles containing 100 mg of cyclosporine per mL NDC 0078-0110-22A dosage syringe is provided for dispensing.Store and Dispense:Sandimmune® Injection (cyclosporine injection, USP)FOR INTRAVENOUS INFUSIONSupplied as a 5 mL sterile ampul containing 50 mg of cyclosporine per mL, in boxes of 10 ampuls…………………………………………………………………..NDC 0078-0109-01Store and Dispense:FOR INFUSION ONLY*Cremophor is the registered trademark of BASF Aktiengesellschaft.Distributed by:Novartis Pharmaceuticals CorporationEast Hanover, New Jersey 07936© NovartisT2015-46March 2015Sandimmune Soft Gelatin Capsules (cyclosporine capsules, USP)25 mg: 3 blister cards of 10 capsules………………………………………………………….NDC 0078-0240-15100 mg: 3 blister cards of 10 capsules………………………………………………………….NDC 0078-0241-15Store and Dispense:An odor may be detected upon opening the unit dose container, which will dissipate shortly thereafter. This odor does not affect the quality of the product.Sandimmune® Oral Solution (cyclosporine oral solution, USP)Supplied in 50 mL bottles containing 100 mg of cyclosporine per mL NDC 0078-0110-22A dosage syringe is provided for dispensing.Store and Dispense:Sandimmune® Injection (cyclosporine injection, USP)FOR INTRAVENOUS INFUSIONSupplied as a 5 mL sterile ampul containing 50 mg of cyclosporine per mL, in boxes of 10 ampuls…………………………………………………………………..NDC 0078-0109-01Store and Dispense:FOR INFUSION ONLY*Cremophor is the registered trademark of BASF Aktiengesellschaft.Distributed by:Novartis Pharmaceuticals CorporationEast Hanover, New Jersey 07936© NovartisT2015-46March 2015Sandimmune Soft Gelatin Capsules (cyclosporine capsules, USP)25 mg: 3 blister cards of 10 capsules………………………………………………………….NDC 0078-0240-15100 mg: 3 blister cards of 10 capsules………………………………………………………….NDC 0078-0241-15Store and Dispense:An odor may be detected upon opening the unit dose container, which will dissipate shortly thereafter. This odor does not affect the quality of the product.Sandimmune® Oral Solution (cyclosporine oral solution, USP)Supplied in 50 mL bottles containing 100 mg of cyclosporine per mL NDC 0078-0110-22A dosage syringe is provided for dispensing.Store and Dispense:Sandimmune® Injection (cyclosporine injection, USP)FOR INTRAVENOUS INFUSIONSupplied as a 5 mL sterile ampul containing 50 mg of cyclosporine per mL, in boxes of 10 ampuls…………………………………………………………………..NDC 0078-0109-01Store and Dispense:FOR INFUSION ONLY*Cremophor is the registered trademark of BASF Aktiengesellschaft.Distributed by:Novartis Pharmaceuticals CorporationEast Hanover, New Jersey 07936© NovartisT2015-46March 2015Sandimmune Soft Gelatin Capsules (cyclosporine capsules, USP)25 mg: 3 blister cards of 10 capsules………………………………………………………….NDC 0078-0240-15100 mg: 3 blister cards of 10 capsules………………………………………………………….NDC 0078-0241-15Store and Dispense:An odor may be detected upon opening the unit dose container, which will dissipate shortly thereafter. This odor does not affect the quality of the product.Sandimmune® Oral Solution (cyclosporine oral solution, USP)Supplied in 50 mL bottles containing 100 mg of cyclosporine per mL NDC 0078-0110-22A dosage syringe is provided for dispensing.Store and Dispense:Sandimmune® Injection (cyclosporine injection, USP)FOR INTRAVENOUS INFUSIONSupplied as a 5 mL sterile ampul containing 50 mg of cyclosporine per mL, in boxes of 10 ampuls…………………………………………………………………..NDC 0078-0109-01Store and Dispense:FOR INFUSION ONLY*Cremophor is the registered trademark of BASF Aktiengesellschaft.Distributed by:Novartis Pharmaceuticals CorporationEast Hanover, New Jersey 07936© NovartisT2015-46March 2015Sandimmune Soft Gelatin Capsules (cyclosporine capsules, USP)25 mg: 3 blister cards of 10 capsules………………………………………………………….NDC 0078-0240-15100 mg: 3 blister cards of 10 capsules………………………………………………………….NDC 0078-0241-15Store and Dispense:An odor may be detected upon opening the unit dose container, which will dissipate shortly thereafter. This odor does not affect the quality of the product.Sandimmune® Oral Solution (cyclosporine oral solution, USP)Supplied in 50 mL bottles containing 100 mg of cyclosporine per mL NDC 0078-0110-22A dosage syringe is provided for dispensing.Store and Dispense:Sandimmune® Injection (cyclosporine injection, USP)FOR INTRAVENOUS INFUSIONSupplied as a 5 mL sterile ampul containing 50 mg of cyclosporine per mL, in boxes of 10 ampuls…………………………………………………………………..NDC 0078-0109-01Store and Dispense:FOR INFUSION ONLY*Cremophor is the registered trademark of BASF Aktiengesellschaft.Distributed by:Novartis Pharmaceuticals CorporationEast Hanover, New Jersey 07936© NovartisT2015-46March 2015Sandimmune Soft Gelatin Capsules (cyclosporine capsules, USP)25 mg: 3 blister cards of 10 capsules………………………………………………………….NDC 0078-0240-15100 mg: 3 blister cards of 10 capsules………………………………………………………….NDC 0078-0241-15Store and Dispense:An odor may be detected upon opening the unit dose container, which will dissipate shortly thereafter. This odor does not affect the quality of the product.Sandimmune® Oral Solution (cyclosporine oral solution, USP)Supplied in 50 mL bottles containing 100 mg of cyclosporine per mL NDC 0078-0110-22A dosage syringe is provided for dispensing.Store and Dispense:Sandimmune® Injection (cyclosporine injection, USP)FOR INTRAVENOUS INFUSIONSupplied as a 5 mL sterile ampul containing 50 mg of cyclosporine per mL, in boxes of 10 ampuls…………………………………………………………………..NDC 0078-0109-01Store and Dispense:FOR INFUSION ONLY*Cremophor is the registered trademark of BASF Aktiengesellschaft.Distributed by:Novartis Pharmaceuticals CorporationEast Hanover, New Jersey 07936© NovartisT2015-46March 2015Sandimmune Soft Gelatin Capsules (cyclosporine capsules, USP)25 mg: 3 blister cards of 10 capsules………………………………………………………….NDC 0078-0240-15100 mg: 3 blister cards of 10 capsules………………………………………………………….NDC 0078-0241-15Store and Dispense:An odor may be detected upon opening the unit dose container, which will dissipate shortly thereafter. This odor does not affect the quality of the product.Sandimmune® Oral Solution (cyclosporine oral solution, USP)Supplied in 50 mL bottles containing 100 mg of cyclosporine per mL NDC 0078-0110-22A dosage syringe is provided for dispensing.Store and Dispense:Sandimmune® Injection (cyclosporine injection, USP)FOR INTRAVENOUS INFUSIONSupplied as a 5 mL sterile ampul containing 50 mg of cyclosporine per mL, in boxes of 10 ampuls…………………………………………………………………..NDC 0078-0109-01Store and Dispense:FOR INFUSION ONLY*Cremophor is the registered trademark of BASF Aktiengesellschaft.Distributed by:Novartis Pharmaceuticals CorporationEast Hanover, New Jersey 07936© NovartisT2015-46March 2015Sandimmune Soft Gelatin Capsules (cyclosporine capsules, USP)25 mg: 3 blister cards of 10 capsules………………………………………………………….NDC 0078-0240-15100 mg: 3 blister cards of 10 capsules………………………………………………………….NDC 0078-0241-15Store and Dispense:An odor may be detected upon opening the unit dose container, which will dissipate shortly thereafter. This odor does not affect the quality of the product.Sandimmune® Oral Solution (cyclosporine oral solution, USP)Supplied in 50 mL bottles containing 100 mg of cyclosporine per mL NDC 0078-0110-22A dosage syringe is provided for dispensing.Store and Dispense:Sandimmune® Injection (cyclosporine injection, USP)FOR INTRAVENOUS INFUSIONSupplied as a 5 mL sterile ampul containing 50 mg of cyclosporine per mL, in boxes of 10 ampuls…………………………………………………………………..NDC 0078-0109-01Store and Dispense:FOR INFUSION ONLY*Cremophor is the registered trademark of BASF Aktiengesellschaft.Distributed by:Novartis Pharmaceuticals CorporationEast Hanover, New Jersey 07936© NovartisT2015-46March 2015Sandimmune Soft Gelatin Capsules (cyclosporine capsules, USP)25 mg: 3 blister cards of 10 capsules………………………………………………………….NDC 0078-0240-15100 mg: 3 blister cards of 10 capsules………………………………………………………….NDC 0078-0241-15Store and Dispense:An odor may be detected upon opening the unit dose container, which will dissipate shortly thereafter. This odor does not affect the quality of the product.Sandimmune® Oral Solution (cyclosporine oral solution, USP)Supplied in 50 mL bottles containing 100 mg of cyclosporine per mL NDC 0078-0110-22A dosage syringe is provided for dispensing.Store and Dispense:Sandimmune® Injection (cyclosporine injection, USP)FOR INTRAVENOUS INFUSIONSupplied as a 5 mL sterile ampul containing 50 mg of cyclosporine per mL, in boxes of 10 ampuls…………………………………………………………………..NDC 0078-0109-01Store and Dispense:FOR INFUSION ONLY*Cremophor is the registered trademark of BASF Aktiengesellschaft.Distributed by:Novartis Pharmaceuticals CorporationEast Hanover, New Jersey 07936© NovartisT2015-46March 2015Sandimmune Soft Gelatin Capsules (cyclosporine capsules, USP)25 mg: 3 blister cards of 10 capsules………………………………………………………….NDC 0078-0240-15100 mg: 3 blister cards of 10 capsules………………………………………………………….NDC 0078-0241-15Store and Dispense:An odor may be detected upon opening the unit dose container, which will dissipate shortly thereafter. This odor does not affect the quality of the product.Sandimmune® Oral Solution (cyclosporine oral solution, USP)Supplied in 50 mL bottles containing 100 mg of cyclosporine per mL NDC 0078-0110-22A dosage syringe is provided for dispensing.Store and Dispense:Sandimmune® Injection (cyclosporine injection, USP)FOR INTRAVENOUS INFUSIONSupplied as a 5 mL sterile ampul containing 50 mg of cyclosporine per mL, in boxes of 10 ampuls…………………………………………………………………..NDC 0078-0109-01Store and Dispense:FOR INFUSION ONLY*Cremophor is the registered trademark of BASF Aktiengesellschaft.Distributed by:Novartis Pharmaceuticals CorporationEast Hanover, New Jersey 07936© NovartisT2015-46March 2015Sandimmune Soft Gelatin Capsules (cyclosporine capsules, USP)25 mg: 3 blister cards of 10 capsules………………………………………………………….NDC 0078-0240-15100 mg: 3 blister cards of 10 capsules………………………………………………………….NDC 0078-0241-15Store and Dispense:An odor may be detected upon opening the unit dose container, which will dissipate shortly thereafter. This odor does not affect the quality of the product.Sandimmune® Oral Solution (cyclosporine oral solution, USP)Supplied in 50 mL bottles containing 100 mg of cyclosporine per mL NDC 0078-0110-22A dosage syringe is provided for dispensing.Store and Dispense:Sandimmune® Injection (cyclosporine injection, USP)FOR INTRAVENOUS INFUSIONSupplied as a 5 mL sterile ampul containing 50 mg of cyclosporine per mL, in boxes of 10 ampuls…………………………………………………………………..NDC 0078-0109-01Store and Dispense:FOR INFUSION ONLY*Cremophor is the registered trademark of BASF Aktiengesellschaft.Distributed by:Novartis Pharmaceuticals CorporationEast Hanover, New Jersey 07936© NovartisT2015-46March 2015Sandimmune Soft Gelatin Capsules (cyclosporine capsules, USP)25 mg: 3 blister cards of 10 capsules………………………………………………………….NDC 0078-0240-15100 mg: 3 blister cards of 10 capsules………………………………………………………….NDC 0078-0241-15Store and Dispense:An odor may be detected upon opening the unit dose container, which will dissipate shortly thereafter. This odor does not affect the quality of the product.Sandimmune® Oral Solution (cyclosporine oral solution, USP)Supplied in 50 mL bottles containing 100 mg of cyclosporine per mL NDC 0078-0110-22A dosage syringe is provided for dispensing.Store and Dispense:Sandimmune® Injection (cyclosporine injection, USP)FOR INTRAVENOUS INFUSIONSupplied as a 5 mL sterile ampul containing 50 mg of cyclosporine per mL, in boxes of 10 ampuls…………………………………………………………………..NDC 0078-0109-01Store and Dispense:FOR INFUSION ONLY*Cremophor is the registered trademark of BASF Aktiengesellschaft.Distributed by:Novartis Pharmaceuticals CorporationEast Hanover, New Jersey 07936© NovartisT2015-46March 2015
Clinical Information
Chemical Structure
No Image foundClinical Pharmacology
Cyclosporine is a potent immunosuppressive agent which in animals prolongs survival of allogeneic transplants involving skin, heart, kidney, pancreas, bone marrow, small intestine, and lung. Cyclosporine has been demonstrated to suppress some humoral immunity and to a greater extent, cell-mediated reactions such as allograft rejection, delayed hypersensitivity, experimental allergic encephalomyelitis, Freund’s adjuvant arthritis, and graft vs. host disease in many animal species for a variety of organs.
Successful kidney, liver, and heart allogeneic transplants have been performed in man using cyclosporine.
The exact mechanism of action of cyclosporine is not known. Experimental evidence suggests that the effectiveness of cyclosporine is due to specific and reversible inhibition of immunocompetent lymphocytes in the G- or G-phase of the cell cycle. T-lymphocytes are preferentially inhibited. The T-helper cell is the main target, although the T-suppressor cell may also be suppressed. Cyclosporine also inhibits lymphokine production and release including interleukin-2 or T-cell growth factor (TCGF).
No functional effects on phagocytic (changes in enzyme secretions not altered, chemotactic migration of granulocytes, macrophage migration, carbon clearance ) or tumor cells (growth rate, metastasis) can be detected in animals. Cyclosporine does not cause bone marrow suppression in animal models or man.
The absorption of cyclosporine from the gastrointestinal tract is incomplete and variable. Peak concentrations (C) in blood and plasma are achieved at about 3.5 hours. C and area under the plasma or blood concentration/time curve (AUC) increase with the administered dose; for blood, the relationship is curvilinear (parabolic) between 0 and 1400 mg. As determined by a specific assay, C is approximately 1.0 ng/mL/mg of dose for plasma and 2.7 to 1.4 ng/mL/mg of dose for blood (for low to high doses). Compared to an intravenous infusion, the absolute bioavailability of the oral solution is approximately 30% based upon the results in 2 patients. The bioavailability of Sandimmune Soft Gelatin Capsules (cyclosporine capsules, USP) is equivalent to Sandimmune Oral Solution, (cyclosporine oral solution, USP).
Cyclosporine is distributed largely outside the blood volume. In blood, the distribution is concentration dependent. Approximately 33% to 47% is in plasma, 4% to 9% in lymphocytes, 5% to 12% in granulocytes, and 41% to 58% in erythrocytes. At high concentrations, the uptake by leukocytes and erythrocytes becomes saturated. In plasma, approximately 90% is bound to proteins, primarily lipoproteins.
The disposition of cyclosporine from blood is biphasic with a terminal half-life of approximately 19 hours (range: 10 to 27 hours). Elimination is primarily biliary with only 6% of the dose excreted in the urine.
Cyclosporine is extensively metabolized but there is no major metabolic pathway. Only 0.1% of the dose is excreted in the urine as unchanged drug. Of 15 metabolites characterized in human urine, 9 have been assigned structures. The major pathways consist of hydroxylation of the Cγ-carbon of 2 of the leucine residues, Cη-carbon hydroxylation, and cyclic ether formation (with oxidation of the double bond) in the side chain of the amino acid 3-hydroxyl-,4-dimethyl-L-2-amino-6-octenoic acid and -demethylation of -methyl leucine residues. Hydrolysis of the cyclic peptide chain or conjugation of the aforementioned metabolites do not appear to be important biotransformation pathways.
Specific Populations
Renal Impairment
In a study performed in 4 subjects with end-stage renal disease (creatinine clearance <5mL/min), an intravenous infusion of 3.5 mg/kg of cyclosporine over 4 hours administered at the end of a hemodialysis session resulted in a mean volume of distribution (Vdss) of 3.49 L/kg and systemic clearance (CL) of 0.369 L/hr/kg. This systemic CL (0.369 L/hr/kg) was approximately two thirds of the mean systemic CL (0.56 L/hr/kg) of cyclosporine in historical control subjects with normal renal function. In 5 liver transplant patients, the mean clearance of cyclosporine on and off hemodialysis was 463 mL/min and 398 mL/min, respectively. Less than 1% of the dose of cyclosporine was recovered in the dialysate.
Hepatic Impairment
Cyclosporine is extensively metabolized by the liver. Since severe hepatic impairment may result in significantly increased cyclosporine exposures, the dosage of cyclosporine may need to be reduced in these patients.
Non-Clinical Toxicology
Sandimmune Injection (cyclosporine injection, USP) is contraindicated in patients with a hypersensitivity to Sandimmune (cyclosporine) and/or Cremophor EL (polyoxyethylated castor oil).Kidney, Liver, and Heart Transplant
(See BOXED WARNING): Sandimmune (cyclosporine), when used in high doses, can cause hepatotoxicity and nephrotoxicity.
Nephrotoxicity
It is not unusual for serum creatinine and BUN levels to be elevated during Sandimmune (cyclosporine) therapy. These elevations in renal transplant patients do not necessarily indicate rejection, and each patient must be fully evaluated before dosage adjustment is initiated.
Nephrotoxicity has been noted in 25% of cases of renal transplantation, 38% of cases of cardiac transplantation, and 37% of cases of liver transplantation. Mild nephrotoxicity was generally noted 2 to 3 months after transplant and consisted of an arrest in the fall of the preoperative elevations of BUN and creatinine at a range of 35 to 45 mg/dl and 2.0 to 2.5 mg/dl, respectively. These elevations were often responsive to dosage reduction.
More overt nephrotoxicity was seen early after transplantation and was characterized by a rapidly rising BUN and creatinine. Since these events are similar to rejection episodes, care must be taken to differentiate between them. This form of nephrotoxicity is usually responsive to Sandimmune (cyclosporine) dosage reduction.
Although specific diagnostic criteria which reliably differentiate renal graft rejection from drug toxicity have not been found, a number of parameters have been significantly associated to one or the other. It should be noted however, that up to 20% of patients may have simultaneous nephrotoxicity and rejection.
A form of chronic progressive cyclosporine-associated nephrotoxicity is characterized by serial deterioration in renal function and morphologic changes in the kidneys. From 5% to 15% of transplant recipients will fail to show a reduction in a rising serum creatinine despite a decrease or discontinuation of cyclosporine therapy. Renal biopsies from these patients will demonstrate an interstitial fibrosis with tubular atrophy. In addition, toxic tubulopathy, peritubular capillary congestion, arteriolopathy, and a striped form of interstitial fibrosis with tubular atrophy may be present. Though none of these morphologic changes is entirely specific, a histologic diagnosis of chronic progressive cyclosporine-associated nephrotoxicity requires evidence of these.
When considering the development of chronic nephrotoxicity it is noteworthy that several authors have reported an association between the appearance of interstitial fibrosis and higher cumulative doses or persistently high circulating trough concentrations of cyclosporine. This is particularly true during the first 6 posttransplant months when the dosage tends to be highest and when, in kidney recipients, the organ appears to be most vulnerable to the toxic effects of cyclosporine. Among other contributing factors to the development of interstitial fibrosis in these patients must be included, prolonged perfusion time, warm ischemia time, as well as episodes of acute toxicity, and acute and chronic rejection. The reversibility of interstitial fibrosis and its correlation to renal function have not yet been determined.
Impaired renal function at any time requires close monitoring, and frequent dosage adjustment may be indicated. In patients with persistent high elevations of BUN and creatinine who are unresponsive to dosage adjustments, consideration should be given to switching to other immunosuppressive therapy. In the event of severe and unremitting rejection, it is preferable to allow the kidney transplant to be rejected and removed rather than increase the Sandimmune (cyclosporine) dosage to a very high level in an attempt to reverse the rejection.
Due to the potential for additive or synergistic impairment of renal function, caution should be exercised when coadministering Sandimmune with other drugs that may impair renal function. (See PRECAUTIONS, Drug Interactions)
Thrombotic Microangiopathy
Occasionally patients have developed a syndrome of thrombocytopenia and microangiopathic hemolytic anemia which may result in graft failure. The vasculopathy can occur in the absence of rejection and is accompanied by avid platelet consumption within the graft as demonstrated by Indium 111 labeled platelet studies. Neither the pathogenesis nor the management of this syndrome is clear. Though resolution has occurred after reduction or discontinuation of Sandimmune (cyclosporine) and 1) administration of streptokinase and heparin or 2) plasmapheresis, this appears to depend upon early detection with Indium 111 labeled platelet scans. (See ADVERSE REACTIONS)
Hyperkalemia
Significant hyperkalemia (sometimes associated with hyperchloremic metabolic acidosis) and hyperuricemia have been seen occasionally in individual patients.
Hepatotoxicity
Cases of hepatotoxicity and liver injury including cholestasis, jaundice, hepatitis, and liver failure have been reported in patients treated with cyclosporine. Most reports included patients with significant co-morbidities, underlying conditions and other confounding factors including infectious complications and comedications with hepatotoxic potential. In some cases, mainly in transplant patients, fatal outcomes have been reported (See ADVERSE REACTIONS, Postmarketing Experience)
Hepatotoxicity, usually manifested by elevations in hepatic enzymes and bilirubin, was reported in patients treated with cyclosporine in clinical trials: 4% in renal transplantation, 7% in cardiac transplantation, and 4% in liver transplantation. This was usually noted during the first month of therapy when high doses of Sandimmune (cyclosporine) were used. The chemistry elevations usually decreased with a reduction in dosage.
Malignancies
As in patients receiving other immunosuppressants, those patients receiving Sandimmune (cyclosporine) are at increased risk for development of lymphomas and other malignancies, particularly those of the skin. The increased risk appears related to the intensity and duration of immunosuppression rather than to the use of specific agents. Because of the danger of oversuppression of the immune system, which can also increase susceptibility to infection, Sandimmune (cyclosporine) should not be administered with other immunosuppressive agents except adrenal corticosteroids. The efficacy and safety of cyclosporine in combination with other immunosuppressive agents have not been determined. Some malignancies may be fatal. Transplant patients receiving cyclosporine are at increased risk for serious infection with fatal outcome.
Serious Infections
Patients receiving immunosuppressants, including Sandimmune, are at increased risk of developing bacterial, viral, fungal, and protozoal infections, including opportunistic infections. These infections may lead to serious, including fatal, outcomes (See BOXED WARNING, and ADVERSE REACTIONS).
Polyoma Virus Infections
Patients receiving immunosuppressants, including Sandimmune, are at increased risk for opportunistic infections, including polyoma virus infections. Polyoma virus infections in transplant patients may have serious, and sometimes, fatal outcomes. These include cases of JC virus-associated progressive multifocal leukoencephalopathy (PML), and polyoma virus-associated nephropathy (PVAN), especially due to BK virus infection, which have been observed in patients receiving cyclosporine.
PVAN is associated with serious outcomes, including deteriorating renal function and renal graft loss, (See ADVERSE REACTIONS/Postmarketing Experience). Patient monitoring may help detect patients at risk for PVAN.
Cases of PML have been reported in patients treated with Sandimmune. PML, which is sometimes fatal, commonly presents with hemiparesis, apathy, confusion, cognitive deficiencies and ataxia. Risk factors for PML include treatment with immunosuppressant therapies and impairment of immune function. In immunosuppressed patients, physicians should consider PML in the differential diagnosis in patients reporting neurological symptoms and consultation with a neurologist should be considered as clinically indicated.
Consideration should be given to reducing the total immunosuppression in transplant patients who develop PML or PVAN. However, reduced immunosuppression may place the graft at risk.
Neurotoxicity
There have been reports of convulsions in adult and pediatric patients receiving cyclosporine, particularly in combination with high-dose methylprednisolone.
Encephalopathy, including Posterior Reversible Encephalopathy Syndrome (PRES), has been described both in postmarketing reports and in the literature. Manifestations include impaired consciousness, convulsions, visual disturbances (including blindness), loss of motor function, movement disorders and psychiatric disturbances. In many cases, changes in the white matter have been detected using imaging techniques and pathologic specimens. Predisposing factors such as hypertension, hypomagnesemia, hypocholesterolemia, high-dose corticosteroids, high cyclosporine blood concentrations, and graft-versus-host disease have been noted in many but not all of the reported cases. The changes in most cases have been reversible upon discontinuation of cyclosporine, and in some cases, improvement was noted after reduction of dose. It appears that patients receiving liver transplant are more susceptible to encephalopathy than those receiving kidney transplant. Another rare manifestation of cyclosporine-induced neurotoxicity is optic disc edema including papilloedema, with possible visual impairment, secondary to benign intracranial hypertension.
Specific Excipients
Anaphylactic Reactions
Rarely (approximately 1 in 1000), patients receiving Sandimmune Injection (cyclosporine injection, USP) have experienced anaphylactic reactions. Although the exact cause of these reactions is unknown, it is believed to be due to the Cremophor EL (polyoxyethylated castor oil) used as the vehicle for the intravenous (IV) formulation. These reactions can consist of flushing of the face and upper thorax, and noncardiogenic pulmonary edema, with acute respiratory distress, dyspnea, wheezing, blood pressure changes, and tachycardia. One patient died after respiratory arrest and aspiration pneumonia. In some cases, the reaction subsided after the infusion was stopped.
Patients receiving Sandimmune Injection (cyclosporine injection, USP) should be under continuous observation for at least the first 30 minutes following the start of the infusion and at frequent intervals thereafter. If anaphylaxis occurs, the infusion should be stopped. An aqueous solution of epinephrine 1:1000 should be available at the bedside as well as a source of oxygen.
Anaphylactic reactions have not been reported with the soft gelatin capsules or oral solution which lack Cremophor EL (polyoxyethylated castor oil). In fact, patients experiencing anaphylactic reactions have been treated subsequently with the soft gelatin capsules or oral solution without incident.
Alcohol (ethanol)
The alcohol content (See DESCRIPTION) of Sandimmune should be taken into account when given to patients in whom alcohol intake should be avoided or minimized, e.g. pregnant or breastfeeding women, in patients presenting with liver disease or epilepsy, in alcoholic patients, or pediatric patients. For an adult weighing 70 kg, the maximum daily oral dose would deliver about 1 gram of alcohol which is approximately 6% of the amount of alcohol contained in a standard drink. The daily intravenous dose would deliver approximately 15% of the amount of alcohol contained in a standard drink.
Care should be taken in using Sandimmune (cyclosporine) with nephrotoxic drugs. (See PRECAUTIONS)
Conversion from Neoral to Sandimmune
Because Sandimmune (cyclosporine) is not bioequivalent to Neoral, conversion from Neoral to Sandimmune (cyclosporine) using a 1:1 ratio (mg/kg/day) may result in a lower cyclosporine blood concentration. Conversion from Neoral to Sandimmune (cyclosporine) should be made with increased blood concentration monitoring to avoid the potential of underdosing.
Concomitant administration of a loop diuretic had no effect on the calcium-lowering action of pamidronate disodium.
Caution is indicated when Pamidronate disodium USP is used with other potentially nephrotoxic drugs.
In multiple myeloma patients, the risk of renal function deterioration may be increased when Pamidronate disodium USP is used in combination with thalidomide.
Patients with malabsorption may have difficulty in achieving therapeutic concentrations with Sandimmune Soft Gelatin Capsules or Oral Solution.
Hypertension
Hypertension is a common side effect of Sandimmune (cyclosporine) therapy. (See ADVERSE REACTIONS) Mild or moderate hypertension is more frequently encountered than severe hypertension and the incidence decreases over time. Antihypertensive therapy may be required. Control of blood pressure can be accomplished with any of the common antihypertensive agents. However, since cyclosporine may cause hyperkalemia, potassium-sparing diuretics should not be used. While calcium antagonists can be effective agents in treating cyclosporine-associated hypertension, care should be taken since interference with cyclosporine metabolism may require a dosage adjustment. (See Drug Interactions)
Vaccination
During treatment with Sandimmune (cyclosporine), vaccination may be less effective and the use of live attenuated vaccines should be avoided.
The principal adverse reactions of Sandimmune (cyclosporine) therapy are renal dysfunction, tremor, hirsutism, hypertension, and gum hyperplasia.
Hypertension
Hypertension, which is usually mild to moderate, may occur in approximately 50% of patients following renal transplantation and in most cardiac transplant patients.
Glomerular Capillary Thrombosis
Glomerular capillary thrombosis has been found in patients treated with cyclosporine and may progress to graft failure. The pathologic changes resemble those seen in the hemolytic-uremic syndrome and include thrombosis of the renal microvasculature, with platelet-fibrin thrombi occluding glomerular capillaries and afferent arterioles, microangiopathic hemolytic anemia, thrombocytopenia, and decreased renal function. Similar findings have been observed when other immunosuppressives have been employed post transplantation.
Hypomagnesemia
Hypomagnesemia has been reported in some, but not all, patients exhibiting convulsions while on cyclosporine therapy. Although magnesium-depletion studies in normal subjects suggest that hypomagnesemia is associated with neurologic disorders, multiple factors, including hypertension, high-dose methylprednisolone, hypocholesterolemia, and nephrotoxicity associated with high plasma concentrations of cyclosporine appear to be related to the neurological manifestations of cyclosporine toxicity.
Clinical Studies
The following reactions occurred in 3% or greater of 892 patients involved in clinical trials of kidney, heart, and liver transplants:
The following reactions occurred in 2% or less of patients: allergic reactions, anemia, anorexia, confusion, conjunctivitis, edema, fever, brittle fingernails, gastritis, hearing loss, hiccups, hyperglycemia, muscle pain, peptic ulcer, thrombocytopenia, tinnitus.
The following reactions occurred rarely: anxiety, chest pain, constipation, depression, hair breaking, hematuria, joint pain, lethargy, mouth sores, myocardial infarction, night sweats, pancreatitis, pruritus, swallowing difficulty, tingling, upper GI bleeding, visual disturbance, weakness, weight loss.
Patients receiving immunosuppressive therapies, including cyclosporine and cyclosporine -containing regimens, are at increased risk of infections (viral, bacterial, fungal, parasitic). Both generalized and localized infections can occur. Pre-existing infections may also be aggravated. Fatal outcomes have been reported. (See WARNINGS)
*Some patients also received ALG.
Cremophor EL (polyoxyethylated castor oil) is known to cause hyperlipemia and electrophoretic abnormalities of lipoproteins. These effects are reversible upon discontinuation of treatment but are usually not a reason to stop treatment.
Reference
This information is obtained from the National Institute of Health's Standard Packaging Label drug database.
"https://dailymed.nlm.nih.gov/dailymed/"
While we update our database periodically, we cannot guarantee it is always updated to the latest version.
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Clonazepam Description Each single-scored tablet, for oral administration, contains 0.5 mg, 1 mg, or 2 mg Clonazepam, USP, a benzodiazepine. Each tablet also contains corn starch, lactose monohydrate, magnesium stearate, microcrystalline cellulose, and povidone. Clonazepam tablets USP 0.5 mg contain Yellow D&C No. 10 Aluminum Lake. Clonazepam tablets USP 1 mg contain Yellow D&C No. 10 Aluminum Lake, as well as FD&C Blue No. 1 Aluminum Lake. Chemically, Clonazepam, USP is 5-(o-chlorophenyl)-1,3-dihydro-7-nitro-2H-1,4-benzodiazepin-2-one. It is a light yellow crystalline powder. It has the following structural formula: C15H10ClN3O3 M.W. 315.72Tips
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A total of 440 drugs (1549 brand and generic names) are known to interact with Imbruvica (ibrutinib). 228 major drug interactions (854 brand and generic names) 210 moderate drug interactions (691 brand and generic names) 2 minor drug interactions (4 brand and generic names) Show all medications in the database that may interact with Imbruvica (ibrutinib).