1 vial

$27.60

1 capsule 25mg

$1.19

Neoral, Sandimmun

It is unusual for this medication to be commenced in the ICU.
Patients admitted to the intensive care unit may be on cyclosporin at the time of admission for the following indications:

  • Solid organ transplant rejection prophylaxis

  • Bone marrow transplant rejection prophylaxis

  • inflammatory disorders such as rheumatoid arthritis, uveitis and psoriasis


Note: decisions about indications and dosage of cyclosporin in ICU patients should be made in consultation with the relevant specialty team (Renal, Haematology etc)

IV:
Cyclosporin injection is a concentrate that must be diluted prior to IV infusion. It is an oily, faintly yellow coloured solution that contains polyoxyethylated castor oil 65% w/v, ethanol 33% v/v and with air in vials replaced by nitrogen
Dilute the concentrate 1:20 to 1:100 by volume (eg 50mg in 20-100ml) with compatible IV fluid. Ensure concentrate is well mixed in diluent fluid to reduce risk of an initial bolus of heavier non-solubilised polyoxyethylated castor oil, which carries an increased risk of anaphylactoid reactions. Diluted solution for infusion is clear and oily. Visually inspect infusion concentrated and infusion solution for particulate matter and / or discolouration.
Administer diluted infusion solution over 2-6 hours
Compatible with normal saline and 5% glucose
Use glass containers or 5% glucose in EXCEL containers (non PVC)
Do not mix with other fluids or medications
Discard any remaining concentrate after preparation of required dose
Discard any diluted fluid not used within 24 hours of preparation
Store at room temperature. Protect from light.

PO:
Neoral 25mg, 50mg and 100mg capsules
Neoral oral solution (100mg/ml)


ADULT DOSE

Dosing should be titrated based on clinical assessments of rejection and tolerability and is generally directed by the primary team responsible for the transplant (eg haematology, renal etc)

IV:
Dose varies according to indication but is generally in the range of 1-5mg/kg/day

PO:
Dosage varies according to indication but is generally in the range of 3-15mg/kg/day

Note: Recommended IV dosage is approximately one-third of oral dosage
See
Laboratory Tests for information about therapeutic drug monitoring which is mandatory

PAEDIATRIC DOSE
Seek specialist paediatric advice

DOSAGE IN RENAL FAILURE AND RENAL REPLACEMENT THERAPY
Dose reduction is generally required and is based on therapeutic drug monitoring (see
Laboratory Tests for information about therapeutic drug monitoring)

Cyclosporin is a potent immunosuppressive agent that prolongs survival of allogeneic transplants involving kidney, liver, heart, pancreas, bone marrow, small intestine, and lung.

CONTRAINDICATIONS:

  • Hypersensitivity to cyclosporin

  • Uncontrolled hypertension

  • Malignancy


WARNINGS
Increased susceptibility to infection and the possible development of lymphoma and other neoplasms may result from the degree of immunosuppression in patients treated with cyclosporin.

Cyclosporin can cause systemic hypertension and nephrotoxicity. The risk increases with increasing dose and duration of cyclosporin therapy.

Cyclosporin can cause nephrotoxicity and hepatotoxicity. The risk increases with increasing doses.

PRECAUTIONS
General
During treatment with cyclosporin, vaccination may be less effective; and the use of live attenuated vaccines should be avoided.

Laboratory Tests:
Cyclosporin has a narrow therapeutic index and variable pharmacokinetics and so monitoring of therapy is mandatory in the critically ill. It is usually appropriate to monitor levels twice weekly.

Two strategies are used for monitoring, one based on trough sampling, i.e. the concentration of drug found within 1 hour before the next dose (termed C0), and the other on the concentration of drug found 2 hours after the dose is given (termed C2).

C0 sampling has been widely used although it appears that C0 is only a weak indicator of absorption of drug. Moreover, the results are assay-dependent as samples of this type contain a large proportion of metabolite that may interfere.

C2 sampling is advantageous in that C2 is an acceptable surrogate for absorption (measured as the area under the concentration-time curve). Moreover, most of the measured drug found at this time is parent drug, making the measurement relatively free of interference from metabolites. A disadvantage of C2 is the need for samples to be taken close to the 2-hour time-point (+ or -15 minutes).

Factors affecting the target ranges for treatment include time of sampling (C0 or C2), organ transplanted, time since transplantation, and other medications. More specific recommended target concentrations for transplant patients are as follows. They may vary in individual cases on the basis of age, gender, renal function, number of episodes of rejection, and concomitant immunosuppressive medication.

Target trough (C0) ranges are as follows:
Liver:
Induction 225-300 ng/mL
Maintenance
100-150 ng/mL
Heart:
Induction 250-325 ng/mL
Maintenance
125-175 ng/mL
Kidney:
Induction 150-225 ng/mL
Maintenance
100-180 ng/mL
Bone Marrow:
Induction 95-205 ng/mL
Maintenance
95-205 ng/mL
Autoimmune indications:
Induction 150-200 ng/mL
Maintenance
100-150 ng/mL

Target C2 ranges are as follows:
Liver:
0-3 months post transplant 800-1200 ng/mL
3-6 months post transplant
640-960 ng/mL
>6 months post transplant
480-720 ng/mL
Renal:
1 months post transplant 1360-2040 ng/mL
2 months post transplant
1200-1800 ng/mL
3 months post transplant
1040-1560 ng/mL
4-6 months post transplant
880-1320 ng/mL
7-12 months post transplant
720-1080 ng/mL
>12 months post transplant
640-960 ng/mL
Lung:
0-2 days post transplant >800
1-7 days post transplant
1200
1-4 weeks post transplant
1200-1700
2 months post transplant
1000-1500
3 months post transplant
800-1200
4-6 months post transplant
700-1000
7-12 months post transplant
600-900
>12 months post transplant
600-800

Note: samples for trough (C0) therapeutic monitoring should be collected in an EDTA (Purple tube) taken one hour before the next dose is due; samples for C2 monitoring should be taken 2 hours +/-15 minutes after the most recent dose

Drug/Laboratory Test Interactions:
Nil of note

All of the individual drugs cited below are well substantiated to interact with cyclosporin

Drugs That May Potentiate Renal Dysfunction
Antibiotics:
Gentamicin, tobramycin, vancomycin, trimethoprim with sulfamethoxazole.
Antineoplastics:
Melphalan.
Antifungals:
Amphotericin B, ketoconazole.
Anti-Inflammatory Drugs:
Azapropazon, diclofenac, naproxen, sulindac, colchicine.
Gastrointestinal Agents:
Cimetidine, ranitidine.
Immunosuppressives:
Tacrolimus.

Drugs That Alter Cyclosporin Concentrations
Cyclosporin is extensively metabolized cytochrome P-450 3A. Substances that inhibit this enzyme could decrease metabolism and increase cyclosporin concentrations. Substances that are inducers of cytochrome P-450 activity could increase metabolism and decrease cyclosporin concentrations. Monitoring of circulating cyclosporin concentrations and appropriate dosage adjustment are essential when these drugs are used concomitantly.
Drugs That Increase Cyclosporin Concentrations
Calcium Channel Blockers:
Diltiazem, nicardipine, verapamil.
Antifungals:
Fluconazole, itraconazole, ketoconazole.
Antibiotics:
Clarithromycin, erythromycin, quinupristin/daldopristin.
Glucocorticoids:
Methylprednisolone.
Other Drugs:
Allopurinol, bromocriptine, danazol, metoclopramide, colchicine, amiodarone.

The HIV protease inhibitors (e.g., indinavir, nelfinavir, ritonavir, and saquinavir) are known to inhibit cytochrome P-450 3A and thus could potentially increase the concentrations of cyclosporin, however no formal studies of the interaction are available. Care should be exercised when these drugs are administered concomitantly.

Drugs/Dietary Supplements That Decrease Cyclosporin Concentrations
Antibiotics:
Nafcillin, rifampin.
Anticonvulsants:
Carbamazepine, phenobarbital, phenytoin.
Other Drugs:
Octreotide, ticlopidine, orlistat, St. John's Wort.

Other Drug Interactions
Cyclosporin may reduce the clearance of digoxin, colchicine, prednisolone and HMG-CoA reductase inhibitors (statins). Severe digitalis toxicity has been seen within days of starting cyclosporin in several patients taking digoxin. There are also reports on the potential of cyclosporin to enhance the toxic effects of colchicine such as myopathy and neuropathy, especially in patients with renal dysfunction.
Cyclosporin should not be used with potassium-sparing diuretics because hyperkalaemia can occur.

Central nervous system:
Tremor, convulsions, headache, paraesthesia
Cardiovascular system:
Hypertension, arrhythmia
Gastrointestinal system:
Stomatitis, gum hyperplasia, diarrhoea, nausea/vomiting, hepatotoxicity, abdominal discomfort
Haematological system:
Leukopaenia, Lymphoma
Urogenital system:
Renal failure
Endocrine system
Hirsutism, Gynecomastia
Musculoskeletal system:
Cramps
Metabolic system:
Hypomagnesaemia

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