Cyclosporine Solution
Loading...Cyclosporine Solution Recall
Get an alert when a recall is issued.
Questions & Answers
Side Effects & Adverse Reactions
(See boxed WARNINGs): Cyclosporine, when used in high doses, can cause hepatotoxicity and nephrotoxicity.
It is not unusual for serum creatinine and BUN levels to be elevated during 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 2–3 months after transplant and consisted of an arrest in the fall of the preoperative elevations of BUN and creatinine at a range of 35–45 mg/dL and 2.0–2.5 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 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.
| Nephrotoxicity vs. Rejection | ||
|---|---|---|
| Parameter | Nephrotoxicity | Rejection |
|
||
| History | Donor > 50 years old or hypotensive Prolonged kidney preservation Prolonged anastomosis time Concomitant nephrotoxic drugs |
Antidonor immune response Retransplant patient |
| Clinical | Often > 6 weeks postop* Prolonged initial nonfunction (acute tubular necrosis) |
Often < 4 weeks postop* Fever > 37.5°C Weight gain > 0.5 kg Graft swelling and tenderness Decrease in daily urine volume > 500 mL (or 50%) |
| Laboratory | CyA serum trough level > 200 ng/mL Gradual rise in Cr ( < 0.15 mg/dL/day)† Cr plateau < 25% above baseline BUN/Cr ≥ 20 |
CyA serum trough level < 150 ng/mL Rapid rise in Cr ( > 0.3 mg/dL/day)† Cr > 25% above baseline BUN/Cr < 20 |
| Biopsy | Arteriolopathy (medial hypertrophy†, hyalinosis, nodular deposits, intimal thickening, endothelial vacuolization, progressive scarring) | Endovasculitis‡ (proliferation† , intimal arteritis*, necrosis, sclerosis) |
| Tubular atrophy, isometric vacuolization, isolated calcifications | Tubulitis with RBC* and WBC* casts, some irregular vacuolization | |
| Minimal edema | Interstitial edema‡ and hemorrhage* | |
| Mild focal infiltrates‡ | Diffuse moderate to severe mononuclear infiltrates§ | |
| Diffuse interstitial fibrosis, often striped form | Glomerulitis (mononuclear cells)‡ | |
| Aspiration Cytology | CyA deposits in tubular and endothelial cells Fine isometric vacuolization of tubular cells |
Inflammatory infiltrate with mononuclear phagocytes, macrophages, lymphoblastoid cells, and activated T-cells These strongly express HLA-DR antigens |
| Urine Cytology | Tubular cells with vacuolization and granularization | Degenerative tubular cells, plasma cells, and lymphocyturia > 20% of sediment |
| Manometry | Intracapsular pressure < 40 mm Hg* | Intracapsular pressure > 40 mm Hg* |
| Ultra-sonography | Unchanged graft cross-sectional area | Increase in graft cross-sectional area AP diameter ≥ Transverse diameter |
| Magnetic Resonance Imagery | Normal appearance | Loss of distinct corticomedullary junction, swelling, image intensity of parachyma approaching that of psoas, loss of hilar fat |
| Radionuclide Scan | Normal or generally decreased perfusion Decrease in tubular function (131 I-hippuran) > decrease in perfusion |
Patchy arterial flow Decrease in perfusion > decrease in tubular function |
| (99m Tc DTPA) | Increased uptake of Indium 111 labeled platelets or Tc-99m in colloid | |
| Therapy | Responds to decreased cyclosporine | Responds to increased steroids or antilymphocyte globulin |
A form of chronic progressive cyclosporine-associated nephrotoxicity is characterized by serial deterioration in renal function and morphologic changes in the kidneys. From 5%–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 levels 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 cyclosporine dosage to a very high level in an attempt to reverse the rejection.
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 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.)
Significant hyperkalemia (sometimes associated with hyperchloremic metabolic acidosis) and hyperuricemia have been seen occasionally in individual patients.
Hepatotoxicity has been noted in 4% of cases of renal transplantation, 7% of cases of cardiac transplantation, and 4% of cases of liver transplantation. This was usually noted during the first month of therapy when high doses of cyclosporine were used and consisted of elevations of hepatic enzymes and bilirubin. The chemistry elevations usually decreased with a reduction in dosage.
As in patients receiving other immunosuppressants, those patients receiving 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, 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.
Immunosuppressed patients are at increased risk for opportunistic infections, including activation of latent viral infections. These include BK virus-associated nephropathy which has been observed in patients receiving immunosuppressants, including cyclosporine. This infection is associated with serious outcomes, including deteriorating renal function and renal graft loss. Patient monitoring may help detect patients at risk for BK virus-associated nephropathy. Reduction in immunosuppression should be considered for patients who develop evidence of BK virus-associated nephropathy.
There have been reports of convulsions in adult and pediatric patients receiving cyclosporine, particularly in combination with high-dose methylprednisolone.
Encephalopathy 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.
Anaphylactic reactions have not been reported with the oral solution which lacks polyoxyethylated castor oil. In fact, patients experiencing anaphylactic reactions have been treated subsequently with the oral solution without incident.
Care should be taken in using cyclosporine with nephrotoxic drugs. (See PRECAUTIONS.)
Because cyclosporine is not bioequivalent to Neoral®1(cyclosporine [MODIFIED]), conversion from Neoral®1 (cyclosporine [MODIFIED]) to cyclosporine using a 1:1 ratio (mg/kg/day) may result in a lower cyclosporine blood concentration. Conversion from Neoral®1 (cyclosporine [MODIFIED]) to cyclosporine should be made with increased blood concentration monitoring to avoid the potential of underdosing.
Legal Issues
There is currently no legal information available for this drug.
FDA Safety Alerts
There are currently no FDA safety alerts available for this drug.
Manufacturer Warnings
There is currently no manufacturer warning information available for this drug.
FDA Labeling Changes
There are currently no FDA labeling changes available for this drug.
Uses
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, cyclosporine injection, USP should be reserved for patients who are unable to take the soft gelatin capsules or oral solution.
History
There is currently no drug history available for this drug.
Other Information
Cyclosporine, the active principle in Cyclosporine Oral Solution, USP is a cyclic polypeptide immunosuppressant agent consisting of 11 amino acids. It is produced as a metabolite by the fungus species Beauveria nivea.
Chemically, cyclosporine is designated as [R-[R*,R*-(E)]]-cyclic(L-alanyl-D-alanyl-N-methyl-L- leucyl-N-methyl-L-leucyl-N-methyl-L-valyl-3-hydroxy-N,4-dimethyl-L-2-amino-6-octenoyl-L-α-aminobutyryl-N-methylglycyl-N-methyl-L-leucyl-L-valyl-N-methyl-L-leucyl).
Cyclosporine Oral Solution, USP is available in 50 mL bottles.
Each mL contains:
Cyclosporine, USP . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 100 mg
Alcohol . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12.5% by volume
Dissolved in an olive oil, NF/Labrafil M 1944 CS (polyoxyethylated oleic glycerides) vehicle which must be further diluted with milk, chocolate milk, or orange juice before oral administration.
The chemical structure of cyclosporine (also known as cyclosporine A) is:
Sources
Cyclosporine Solution Manufacturers
-
Morton Grove Pharmaceuticals, Inc.
![Cyclosporine Solution [Morton Grove Pharmaceuticals, Inc.]](/wp-content/themes/bootstrap/assets/img/loading2.gif)
Cyclosporine Solution | Morton Grove Pharmaceuticals, Inc.
Cyclosporine Oral Solution, USP has decreased bioavailability in comparison to Neoral®1 soft gelatin capsules (cyclosporine capsules, USP) MODIFIED and Neoral®1 oral solution (cyclosporine oral solution, USP) MODIFIED. Cyclosporine and Neoral®1 (cyclosporine [MODIFIED]) are not bioequivalent and cannot be used interchangeably without physician supervision.
The initial oral dose of 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 renal transplant patients without an apparent rise in rejection rate.
(See Blood Level Monitoring below).
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 mg/kg/day for the first 4 days tapered to 1 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 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. Cyclosporine oral solution should be administered on a consistent schedule with regard to time of day and relation to meals.
Take the prescribed amount of 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.
Blood Level MonitoringSeveral study centers have found blood level monitoring of cyclosporine useful in patient management. While no fixed relationships have yet been established, in one series of 375 consecutive cadaveric renal transplant recipients, dosage was adjusted to achieve specific whole blood 24-hour trough levels of 100–200 ng/mL as determined by high-pressure liquid chromatography (HPLC).
Of major importance to blood level analysis is the type of assay used. The above levels are specific to the parent cyclosporine molecule and correlate directly to the new monoclonal specific radioimmunoassays (mRIA-sp). Nonspecific assays are also available which detect the parent compound molecule and various of its metabolites. Older studies often cited levels using a nonspecific assay which were roughly twice those of specific assays. Assay results are not interchangeable and their use should be guided by their approved labeling. If plasma specimens are employed, levels will vary with the temperature at the time of separation from whole blood. Plasma levels may range from 1/2–1/5 of whole blood levels. Refer to individual assay labeling for complete instructions. In addition, Transplantation Proceedings (June 1990) contains position papers and a broad consensus generated at the Cyclosporine-Therapeutic Drug Monitoring conference that year. Blood level monitoring is not a replacement for renal function monitoring or tissue biopsies.
-
Ivax Pharmaceuticals, Inc.
Cyclosporine Solution | Ivax Pharmaceuticals, Inc.
Cyclosporine Oral Solution USP MODIFIED has increased bioavailability in comparison to Sandimmune (Cyclosporine Oral Solution USP). Cyclosporine Oral Solution USP MODIFIED and Sandimmune (Cyclosporine Oral Solution USP) are not bioequivalent and cannot be used interchangeably without physician supervision.
The daily dose of Cyclosporine Oral Solution USP MODIFIED should always be given in two divided doses (BID). It is recommended that Cyclosporine Oral Solution USP MODIFIED be administered on a consistent schedule with regard to time of day and relation to meals. Grapefruit and grapefruit juice affect metabolism, increasing blood concentration of cyclosporine, thus should be avoided.
Specific Populations
Renal Impairment in Kidney, Liver, and Heart Transplantation
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).
Renal Impairment in Rheumatoid Arthritis and Psoriasis
Patients with impaired renal function should not receive cyclosporine (see CONTRAINDICATIONS, 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).
Newly Transplanted Patients
The initial oral dose of Cyclosporine Oral Solution USP MODIFIED can be given 4 to 12 hours prior to transplantation or be given postoperatively. The initial dose of Cyclosporine Oral Solution USP MODIFIED varies depending on the transplanted organ and the other immunosuppressive agents included in the immunosuppressive protocol. In newly transplanted patients, the initial oral dose of Cyclosporine Oral Solution USP MODIFIED is the same as the initial oral dose of Sandimmune (Cyclosporine Oral Solution USP). Suggested initial doses are available from the results of a 1994 survey of the use of Sandimmune (Cyclosporine Oral Solution USP) in US transplant centers. The mean ± SD initial doses were 9 ± 3 mg/kg/day for renal transplant patients (75 centers), 8 ± 4 mg/kg/day for liver transplant patients (30 centers), and 7 ± 3 mg/kg/day for heart transplant patients (24 centers). Total daily doses were divided into two equal daily doses. The Cyclosporine Oral Solution USP MODIFIED dose is subsequently adjusted to achieve a pre-defined cyclosporine blood concentration (see Blood Concentration Monitoring in Transplant Patients, below). If cyclosporine trough blood concentrations are used, the target range is the same for Cyclosporine Oral Solution USP MODIFIED as for Sandimmune (Cyclosporine Oral Solution USP). Using the same trough concentration target range for Cyclosporine Oral Solution USP MODIFIED as for Sandimmune (Cyclosporine Oral Solution USP) results in greater cyclosporine exposure when Cyclosporine Oral Solution USP MODIFIED is administered (see Pharmacokinetics, Absorption). Dosing should be titrated based on clinical assessments of rejection and tolerability. Lower Cyclosporine Oral Solution USP MODIFIED doses may be sufficient as maintenance therapy.
Adjunct therapy with adrenal corticosteroids is recommended initially. Different tapering dosage schedules of prednisone appear to achieve similar results. A representative dosage schedule based on the patient’s weight started with 2 mg/kg/day for the first 4 days tapered to 1 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. Steroid doses may be further tapered on an individualized basis depending on status of patient and function of graft. Adjustments in dosage of prednisone must be made according to the clinical situation.
Conversion from Sandimmune (Cyclosporine Oral Solution USP) to Cyclosporine Oral Solution USP MODIFIED in Transplant Patients
In transplanted patients who are considered for conversion to Cyclosporine Oral Solution USP MODIFIED from Sandimmune (Cyclosporine Oral Solution USP), Cyclosporine Oral Solution USP MODIFIED should be started with the same daily dose as was previously used with Sandimmune (Cyclosporine Oral Solution USP) (1:1 dose conversion). The Cyclosporine Oral Solution USP MODIFIED dose should subsequently be adjusted to attain the pre-conversion cyclosporine blood trough concentration. Using the same trough concentration target range for Cyclosporine Oral Solution USP MODIFIED as for Sandimmune (Cyclosporine Oral Solution USP) results in greater cyclosporine exposure when Cyclosporine Oral Solution USP MODIFIED is administered (see Pharmacokinetics, Absorption). Patients with suspected poor absorption of Sandimmune (Cyclosporine Oral Solution USP) require different dosing strategies (see Transplant Patients with Poor Absorption of Sandimmune (Cyclosporine Oral Solution USP), below). In some patients, the increase in blood trough concentration is more pronounced and may be of clinical significance.
Until the blood trough concentration attains the pre-conversion value, it is strongly recommended that the cyclosporine blood trough concentration be monitored every 4 to 7 days after conversion to Cyclosporine Oral Solution USP MODIFIED. In addition, clinical safety parameters such as serum creatinine and blood pressure should be monitored every two weeks during the first two months after conversion. If the blood trough concentrations are outside the desired range and/or if the clinical safety parameters worsen, the dosage of Cyclosporine Oral Solution USP MODIFIED must be adjusted accordingly.
Transplant Patients with Poor Absorption of Sandimmune (Cyclosporine Oral Solution USP)
Patients with lower than expected cyclosporine blood trough concentrations in relation to the oral dose of Sandimmune (Cyclosporine Oral Solution USP) may have poor or inconsistent absorption of cyclosporine from Sandimmune (Cyclosporine Oral Solution USP). After conversion to Cyclosporine Oral Solution USP MODIFIED, patients tend to have higher cyclosporine concentrations. Due to the increase in bioavailability of cyclosporine following conversion to Cyclosporine Oral Solution USP MODIFIED, the cyclosporine blood trough concentration may exceed the target range. Particular caution should be exercised when converting patients to Cyclosporine Oral Solution USP MODIFIED at doses greater than 10 mg/kg/day. The dose of Cyclosporine Oral Solution USP MODIFIED should be titrated individually based on cyclosporine trough concentrations, tolerability, and clinical response. In this population the cyclosporine blood trough concentration should be measured more frequently, at least twice a week (daily, if initial dose exceeds 10 mg/kg/day) until the concentration stabilizes within the desired range.
Rheumatoid Arthritis
The initial dose of Cyclosporine Oral Solution USP MODIFIED is 2.5 mg/kg/day, taken twice daily as a divided (BID) oral dose. Salicylates, NSAIDs, and oral corticosteroids may be continued (see WARNINGS and PRECAUTIONS, Drug Interactions). Onset of action generally occurs between 4 and 8 weeks. If insufficient clinical benefit is seen and tolerability is good (including serum creatinine less than 30% above baseline), the dose may be increased by 0.5 to 0.75 mg/kg/day after 8 weeks and again after 12 weeks to a maximum of 4 mg/kg/day. If no benefit is seen by 16 weeks of therapy, Cyclosporine Oral Solution USP MODIFIED therapy should be discontinued.
Dose decreases by 25% to 50% should be made at any time to control adverse events, e.g., hypertension elevations in serum creatinine (30% above patient’s pretreatment level) or clinically significant laboratory abnormalities (see WARNINGS and PRECAUTIONS).
If dose reduction is not effective in controlling abnormalities or if the adverse event or abnormality is severe, Cyclosporine Oral Solution USP MODIFIED should be discontinued. The same initial dose and dosage range should be used if Cyclosporine Oral Solution USP MODIFIED is combined with the recommended dose of methotrexate. Most patients can be treated with Cyclosporine Oral Solution USP MODIFIED doses of 3 mg/kg/day or below when combined with methotrexate doses of up to 15 mg/week (see CLINICAL PHARMACOLOGY, Clinical Trials).
There is limited long-term treatment data. Recurrence of rheumatoid arthritis disease activity is generally apparent within 4 weeks after stopping cyclosporine.
Psoriasis
The initial dose of Cyclosporine Oral Solution USP MODIFIED should be 2.5 mg/kg/day. Cyclosporine Oral Solution USP MODIFIED should be taken twice daily, as a divided (1.25 mg/kg BID) oral dose. Patients should be kept at that dose for at least 4 weeks, barring adverse events. If significant clinical improvement has not occurred in patients by that time, the patient’s dosage should be increased at 2 week intervals. Based on patient response, dose increases of approximately 0.5 mg/kg/day should be made to a maximum of 4 mg/kg/day.
Dose decreases by 25% to 50% should be made at any time to control adverse events, e.g., hypertension, elevations in serum creatinine (≥ 25% above the patient’s pretreatment level), or clinically significant laboratory abnormalities. If dose reduction is not effective in controlling abnormalities, or if the adverse event or abnormality is severe, Cyclosporine Oral Solution USP MODIFIED should be discontinued (see Special Monitoring for Psoriasis Patients).
Patients generally show some improvement in the clinical manifestations of psoriasis in 2 weeks. Satisfactory control and stabilization of the disease may take 12 to 16 weeks to achieve. Results of a dose-titration clinical trial with Cyclosporine Oral Solution USP MODIFIED indicate that an improvement of psoriasis by 75% or more (based on PASI) was achieved in 51% of the patients after 8 weeks and in 79% of the patients after 16 weeks. Treatment should be discontinued if satisfactory response cannot be achieved after 6 weeks at 4 mg/kg/day or the patient’s maximum tolerated dose. Once a patient is adequately controlled and appears stable the dose of Cyclosporine Oral Solution USP MODIFIED should be lowered, and the patient treated with the lowest dose that maintains an adequate response (this should not necessarily be total clearing of the patient). In clinical trials, cyclosporine doses at the lower end of the recommended dosage range were effective in maintaining a satisfactory response in 60% of the patients. Doses below 2.5 mg/kg/day may also be equally effective.
Upon stopping treatment with cyclosporine, relapse will occur in approximately 6 weeks (50% of the patients) to 16 weeks (75% of the patients). In the majority of patients rebound does not occur after cessation of treatment with cyclosporine. Thirteen cases of transformation of chronic plaque psoriasis to more severe forms of psoriasis have been reported. There were 9 cases of pustular and 4 cases of erythrodermic psoriasis. Long term experience with Cyclosporine Oral Solution USP MODIFIED in psoriasis patients is limited and continuous treatment for extended periods greater than one year is not recommended. Alternation with other forms of treatment should be considered in the long term management of patients with this life long disease.
Recommendations for Administration
To make Cyclosporine Oral Solution USP MODIFIED more palatable, it should be diluted with orange or apple juice that is at room temperature. Patients should avoid switching diluents frequently. This solution, when mixed with juice, may appear cloudy. Grapefruit juice affects metabolism of cyclosporine and should be avoided. The combination of Cyclosporine Oral Solution USP MODIFIED solution with milk can be unpalatable. The effect of milk on the bioavailability of cyclosporine when administered as Cyclosporine Oral Solution USP MODIFIED has not been evaluated.
Take the prescribed amount of Cyclosporine Oral Solution USP MODIFIED from the container using the dosing syringe supplied, after removal of the protective cover, and transfer the solution to a glass of orange or apple juice. Stir well and drink at once. Do not allow diluted oral solution to stand before drinking. Use a glass container (not plastic). Rinse the glass with more diluent to ensure that the total dose is consumed. After use, dry the outside of the dosing syringe with a clean towel and replace the protective cover. Do not rinse the dosing syringe with water or other cleaning agents. If the syringe requires cleaning, it must be completely dry before resuming use.
Blood Concentration Monitoring in Transplant Patients
Transplant centers have found blood concentration monitoring of cyclosporine to be an essential component of patient management. Of importance to blood concentration analysis are the type of assay used, the transplanted organ, and other immunosuppressant agents being administered. While no fixed relationship has been established, blood concentration monitoring may assist in the clinical evaluation of rejection and toxicity, dose adjustments, and the assessment of compliance.
Various assays have been used to measure blood concentrations of cyclosporine. Older studies using a nonspecific assay often cited concentrations that were roughly twice those of the specific assays. Therefore, comparison between concentrations in the published literature and an individual patient concentration using current assays must be made with detailed knowledge of the assay methods employed. Current assay results are also not interchangeable and their use should be guided by their approved labeling. A discussion of the different assay methods is contained in Annals of Clinical Biochemistry 1994;31:420-446. While several assays and assay matrices are available, there is a consensus that parent-compound-specific assays correlate best with clinical events. Of these, HPLC is the standard reference, but the monoclonal antibody RIAs and the monoclonal antibody FPIA offer sensitivity, reproducibility, and convenience. Most clinicians base their monitoring on trough cyclosporine concentrations. Applied Pharmacokinetics, Principles of Therapeutic Drug Monitoring (1992) contains a broad discussion of cyclosporine pharmacokinetics and drug monitoring techniques. Blood concentration monitoring is not a replacement for renal function monitoring or tissue biopsies.
![Cyclosporine Solution [Ivax Pharmaceuticals, Inc.]](http://dailymed.nlm.nih.gov/dailymed/image.cfm?setid=f3dc2a50-1084-4190-a6f3-37034a04db86&name=12e7bebb-e8cc-45c9-977c-e7631836681d-03.jpg)
Login To Your Free Account