Cyclosporine (Injection)

Cyclosporine (Injection)
Black Box Warning
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Kiran Singh, M.D. [2]

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Black Box Warning

Warning: See full prescribing information for complete Boxed Warning. * Only physicians experienced in immunosuppressive therapy and management of organ transplant patients should prescribe cyclosporine. Patients receiving the drug should be managed in facilities equipped and staffed with adequate laboratory and supportive medical resources. The physician responsible for maintenance therapy should have complete information requisite for the follow-up of the patient. Cyclosporine should be administered with adrenal corticosteroids but not with other immunosuppressive agents. Increased susceptibility to infection and the possible development of lymphoma may result from immunosuppression.

Overview

Cyclosporine (Injection) is a {{{drugClass}}} that is FDA approved for the treatment of {{{indication}}}. There is a Black Box Warning for this drug as shown here. Common adverse reactions include .

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

Indications

• 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 should be reserved for patients who are unable to take the soft gelatin capsules or oral solution.

Dosage

Note: Anaphylactic reactions have occurred with cyclosporine injection.

• Patients unable to take cyclosporine soft gelatin capsules or oral solution pre- or postoperatively may be treated with the IV concentrate. Cyclosporine injection is administered at 1/3 the oral dose. The initial dose of cyclosporine injection should be given 4 to 12 hours prior to transplantation as a single IV dose of 5 to 6 mg/kg/day. This daily single dose is continued postoperatively until the patient can tolerate the soft gelatin capsules or oral solution. Patients should be switched to cyclosporine soft gelatin capsules or oral solution as soon as possible after surgery. In pediatric usage, the same dose and dosing regimen may be used, although higher doses may be required.

• Adjunct steroid therapy is to be used.

• Immediately before use, the IV concentrate should be diluted 1 mL cyclosporine injection in 20 mL to 100 mL 0.9% Sodium Chloride Injection or 5% Dextrose Injection and given in a slow intravenous infusion over approximately 2 to 6 hours.

• Diluted infusion solutions should be discarded after 24 hours.

• The Cremophor® EL (polyoxyethylated castor oil) contained in the concentrate for intravenous infusion can cause phthalate stripping from PVC.

• Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Blood Concentration Monitoring

• Several study centers have found blood concentration 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 concentrations of 100 to 200 ng/mL as determined by high-pressure liquid chromatography (HPLC).

• Of major importance to blood concentration analysis is the type of assay used. The above concentrations 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 concentrations 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, concentrations will vary with the temperature at the time of separation from whole blood. Plasma concentrations may range from 1/2 to 1/5 of whole blood concentrations. 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 concentration monitoring is not a replacement for renal function monitoring or tissue biopsies.

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

Condition1

• Developed by:

• Class of Recommendation:

• Strength of Evidence:

• Dosing Information

• Dosage

Condition2

There is limited information regarding Off-Label Guideline-Supported Use of Cyclosporine (Injection) in adult patients.

Non–Guideline-Supported Use

Condition1

• Dosing Information

• Dosage

Condition2

There is limited information regarding Off-Label Non–Guideline-Supported Use of Cyclosporine (Injection) in adult patients.

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

Condition1

• Dosing Information

• Dosage

Condition2

There is limited information regarding FDA-Labeled Use of Cyclosporine (Injection) in pediatric patients.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

Condition1

• Developed by:

• Class of Recommendation:

• Strength of Evidence:

• Dosing Information

• Dosage

Condition2

There is limited information regarding Off-Label Guideline-Supported Use of Cyclosporine (Injection) in pediatric patients.

Non–Guideline-Supported Use

Condition1

• Dosing Information

• Dosage

Condition2

There is limited information regarding Off-Label Non–Guideline-Supported Use of Cyclosporine (Injection) in pediatric patients.

Contraindications

• Condition1

Warnings

Warning: See full prescribing information for complete Boxed Warning. * Only physicians experienced in immunosuppressive therapy and management of organ transplant patients should prescribe cyclosporine. Patients receiving the drug should be managed in facilities equipped and staffed with adequate laboratory and supportive medical resources. The physician responsible for maintenance therapy should have complete information requisite for the follow-up of the patient. Cyclosporine should be administered with adrenal corticosteroids but not with other immunosuppressive agents. Increased susceptibility to infection and the possible development of lymphoma may result from immunosuppression.

• Description

Precautions

• Description

Adverse Reactions

Clinical Trials Experience

• The principal adverse reactions of 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 posttransplantation.

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 hypomagnesemiansion, 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:

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This image is provided by the National Library of Medicine.

• 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.

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This image is provided by the National Library of Medicine.

• Cyclosporine was discontinued on a temporary basis and then restarted in 18 additional patients.

• 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.

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This image is provided by the National Library of Medicine.

• 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.

Postmarketing Experience

Hepatotoxicity:

• Cases of hepatotoxicity and liver injury including cholestasis, jaundice, hepatitis and liver failure; serious and/or fatal outcomes have been reported.

Increased Risk of Infections:

• Cases of JC virus-associated progressive multifocal leukoencephalopathy (PML), sometimes fatal; and polyoma virus-associated nephropathy (PVAN), especially BK virus resulting in graft loss have been reported.

Headache, including Migraine:

• Cases of migraine have been reported. In some cases, patients have been unable to continue cyclosporine, however, the final decision on treatment discontinuation should be made by the treating physician following the careful assessment of benefits versus risks.

Drug Interactions

• Drug

• Description

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA):

• Pregnancy Category

Pregnancy Category (AUS):

• Australian Drug Evaluation Committee (ADEC) Pregnancy Category

There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Cyclosporine (Injection) in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Cyclosporine (Injection) during labor and delivery.

Nursing Mothers

There is no FDA guidance on the use of Cyclosporine (Injection) with respect to nursing mothers.

Pediatric Use

There is no FDA guidance on the use of Cyclosporine (Injection) with respect to pediatric patients.

Geriatic Use

There is no FDA guidance on the use of Cyclosporine (Injection) with respect to geriatric patients.

Gender

There is no FDA guidance on the use of Cyclosporine (Injection) with respect to specific gender populations.

Race

There is no FDA guidance on the use of Cyclosporine (Injection) with respect to specific racial populations.

Renal Impairment

There is no FDA guidance on the use of Cyclosporine (Injection) in patients with renal impairment.

Hepatic Impairment

There is no FDA guidance on the use of Cyclosporine (Injection) in patients with hepatic impairment.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Cyclosporine (Injection) in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Cyclosporine (Injection) in patients who are immunocompromised.

Administration and Monitoring

Administration

• Oral

• Intravenous

Monitoring

There is limited information regarding Monitoring of Cyclosporine (Injection) in the drug label.

IV Compatibility

There is limited information regarding IV Compatibility of Cyclosporine (Injection) in the drug label.

Overdosage

• There is a minimal experience with overdosage. 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. Cyclosporine is not dialyzable to any great extent, nor is it cleared well by charcoal hemoperfusion. The oral LD 50 is 2329 mg/kg in mice, 1480 mg/kg in rats, and > 1000 mg/kg in rabbits. The IV LD 50 is 148 mg/kg in mice, 104 mg/kg in rats, and 46 mg/kg in rabbits.

Pharmacology

There is limited information regarding Cyclosporine (Injection) Pharmacology in the drug label.

Mechanism of Action

Structure

File:Cyclosporine (Injection)01.png

This image is provided by the National Library of Medicine.

Pharmacodynamics

There is limited information regarding Pharmacodynamics of Cyclosporine (Injection) in the drug label.

Pharmacokinetics

There is limited information regarding Pharmacokinetics of Cyclosporine (Injection) in the drug label.

Nonclinical Toxicology

There is limited information regarding Nonclinical Toxicology of Cyclosporine (Injection) in the drug label.

Clinical Studies

There is limited information regarding Clinical Studies of Cyclosporine (Injection) in the drug label.

How Supplied

• Supplied as a 5 mL sterile ampule containing 50 mg of cyclosporine per mL, in boxes of 10 ampules. (NDC 0574-0866-10)

Storage

• Store at 20°C to 25°C (68°F to 77°F). Protect from light. Discard unused portion.

Images

Drug Images

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Package and Label Display Panel

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Patient Counseling Information

There is limited information regarding Patient Counseling Information of Cyclosporine (Injection) in the drug label.

Precautions with Alcohol

• Alcohol-Cyclosporine (Injection) interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

• CYCLOSPORINE ®

Look-Alike Drug Names

• A® — B®

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.

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