Drugs Details

Drugs Info of Gengraf, Neoral, Sandimmune
Drugs Details
  • Drugs Type  : FDA
  • Date : 26th Jan 2015 03:38 am
  • Brand Name : Gengraf, Neoral, Sandimmune
  • Generic Name : cyclosporine (Pronunciation: SYE kloe SPOR een)
Descriptions

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 Beauveria nivea.

Chemically, cyclosporine is designated as [R-[R*,R*-(E)]]-cyclic(L-alanyl-D-alanyl-N-methyl-L-leucylN-methyl-L-leucyl-N-methyl-L-valyl-3-hydroxy-N,4-dimethyl-L-2-amino-6-octenoyl-L-α-amino-butyrylN-methylglycyl-N-methyl-L-leucyl-L-valyl-N-methyl-L-leucyl).

Sandimmune® Soft Gelatin Capsules (cyclosporine capsules, USP) are available in 25 mg and 100 mg strengths.

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: corn oil, gelatin, iron oxide red, linoleoyl macrogolglycerides, sorbitol, and titanium dioxide. May also contain glycerol. 100 mg capsules may contain iron oxide yellow.

Sandimmune® Oral Solution (cyclosporine oral solution, USP) is available in 50 mL bottles.

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 (cyclosporine injection, USP) is available in a 5 mL sterile ampul for I.V. administration.

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

 

Sandimmune® (cyclosporine capsules, USP)  Structural Formula Illustration

What are the possible side effects of cyclosporine (Gengraf, Neoral, Sandimmune)?

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have a serious side effect such as:

  • fever, sweating, chills, body aches, flu symptoms, sores in your mouth and throat, weight loss;
  • change in your mental state, problems with speech or walking, decreased vision (may start gradually and get worse quickly);
  • easy bruising or bleeding, pale skin, confusion or weakness;
  • feeling light-headed...

Read All Potential Side Effects and See Pictures of Sandimmune »

What are the precautions when taking cyclosporine (Sandimmune)?

Before taking cyclosporine, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

This medication should not be used if you have certain medical conditions. Before using this medicine, consult your doctor or pharmacist if you have: history of chicken pox/shingles, uncontrolled high blood pressure, cancer, skin lesions of unknown cause, current use of radiation therapy (including phototherapy with PUVA or UVB), kidney problems (for arthritis or psoriasis patients only).

Before using this medication, tell your doctor or pharmacist your medical history, especially of: kidney disease, liver...

Read All Potential Precautions of Sandimmune »

This monograph has been modified to include the generic and brand name in many instances.

Indications

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.

Dosage Administration

Sandimmune® Soft Gelatin Capsules (cyclosporine capsules, USP) and Sandimmune® Oral Solution (cyclosporine oral solution, USP)

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 4-12 hours prior to transplantation as a single dose of 15 mg/kg. Although a daily single dose of 14-18 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 10-14 mg/kg/day. The initial single daily dose is continued postoperatively for 1-2 weeks and then tapered by 5% per week to a maintenance dose of 5-10 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 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.

Sandimmune® Injection (cyclosporine injection, USP)

FOR INFUSION ONLY

Note: Anaphylactic reactions have occurred with Sandimmune® Injection (cyclosporine injection, USP). (See WARNINGS)

Patients unable to take Sandimmune® Soft Gelatin Capsules or Oral Solution pre- or postoperatively may be treated with the I.V. concentrate. Sandimmune® Injection (cyclosporine injection, USP) is administered at 1/3 the oral dose. The initial dose of Sandimmune® Injection (cyclosporine injection, USP) should be given 4-12 hours prior to transplantation as a single I.V. dose of 5-6 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 Sandimmune® 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. (See aforementioned.)

Immediately before use, the I.V. concentrate should be diluted 1 mL Sandimmune® Injection (cyclosporine injection, USP) in 20 mL-100 mL 0.9% Sodium Chloride Injection or 5% Dextrose Injection and given in a slow intravenous infusion over approximately 2-6 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 100-200 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 1/2-1/5 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.

How Supplied

Sandimmune® Soft Gelatin Capsules (cyclosporine capsules, USP)

25 mg: Oblong, pink, branded “78/240”. Unit dose packages of 30 capsules, 3 blister cards of 10 capsules………………………….NDC 0078-0240-15

100 mg: Oblong, dusty rose, branded “78/241”. Unit dose packages of 30 capsules, 3 blister cards of 10 capsules………………….NDC 0078-0241-15

Store and Dispense

Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F) [see USP Controlled Room Temperature].

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 0078-0110-22

A dosage syringe is provided for dispensing.

Store and Dispense

In the original container at temperatures below 30°C (86°F). Do not store in the refrigerator. Protect from freezing. Once opened, the contents must be used within 2 months.

Sandimmune® Injection (cyclosporine injection, USP)

FOR INTRAVENOUS INFUSION

Supplied as a 5 mL sterile ampul containing 50 mg of cyclosporine per mL, in boxes of 10 ampuls………………………………..NDC 0078-0109-01 Store and Dispense: At temperatures below 30°C (86°F). Protect from light. FOR INFUSION ONLY

Distributed by: Novartis Pharmaceuticals Corporation East Hanover, New Jersey 07936

This monograph has been modified to include the generic and brand name in many instances.

Side Effects

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 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 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:

 

Body System/Adverse Reactions Randomized Kidney Patients All Sandimmune® (cyclosporine) Patients
Sandimmune®
(N=227) %
Azathioprine
(N=228) %
Kidney
(N=705) %
Heart
(N=112) %
Liver
(N=75) %
Genitourinary
  Renal Dysfunction 32 6 25 38 37
Cardiovascular
  Hypertension 26 18 13 53 27
  Cramps 4 < 1 2 < 1 0
Skin
  Hirsutism 21 < 1 21 28 45
  Acne 6 8 2 2 1
Central Nervous System
  Tremor 12 0 21 31 55
  Convulsions 3 1 1 4 5
  Headache 2 < 1 2 15 4
Gastrointestinal
  Gum Hyperplasia 4 0 9 5 16
  Diarrhea 3 < 1 3 4 8
  Nausea/Vomiting 2 < 1 4 10 4
  Hepatotoxicity < 1 < 1 4 7 4
  Abdominal Discomfort < 1 0 < 1 7 0
Autonomic Nervous System
  Paresthesia 3 0 1 2 1
  Flushing < 1 0 4 0 4
Hematopoietic
  Leukopenia 2 19 < 1 6 0
  Lymphoma < 1 0 1 6 1
Respiratory
  Sinusitis < 1 0 4 3 7
Miscellaneous
  Gynecomastia < 1 0 < 1 4 3

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.

Renal Transplant Patients in Whom Therapy Was Discontinued

View Enlarged Table

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)

Infectious Complications in the Randomized Renal Transplant Patients

Complication Sandimmune® Treatment
(N=227)
% of Complications
Standard Treatment*
(N=228)
% of Complications
Septicemia 5.3 4.8
Abscesses 4.4 5.3
Systemic Fungal Infection 2.2 3.9
Local Fungal Infection 7.5 9.6
Cytomegalovirus 4.8 12.3
Other Viral Infections 15.9 18.4
Urinary Tract Infections 21.1 20.2
Wound and Skin Infections 7.0 10.1
Pneumonia 6.2 9.2
*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.

Postmarketing Experience

Hepatotoxicity

Cases of hepatotoxicity and liver injury including cholestasis, jaundice, hepatitis and liver failure; serious and/or fatal outcomes have been reported. [See WARNINGS, Hepatotoxicity]

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. [See WARNINGS, Polyoma Virus Infection]

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.

Read the Sandimmune (cyclosporine) Side Effects Center for a complete guide to possible side effects

Learn More »

Interactions

Effect of Drugs and Other Agents on Cyclosporine Pharmacokinetics and/or Safety

All of the individual drugs cited below are well substantiated to interact with cyclosporine. In addition, concomitant use of nonsteroidal anti-inflammatory drugs with cyclosporine, particularly in the setting of dehydration, may potentiate renal dysfunction. Caution should be exercised when using other drugs which are known to impair renal function. (See WARNINGS, Nephrotoxicity)

Drugs That May Potentiate Renal Dysfunction

View Enlarged Table

During the concomitant use of a drug that may exhibit additive or synergistic renal impairment potential with cyclosporine, close monitoring of renal function (in particular serum creatinine) should be performed. If a significant impairment of renal function occurs, reduction in the dosage of cyclosporine and/or co-administered drug or an alternative treatment should be considered.

Cyclosporine is extensively metabolized by CYP 3A isoenzymes, in particular CYP3A4, and is a substrate of the multidrug efflux transporter P-glycoprotein. Various agents are known to either increase or decrease plasma or whole blood concentrations of cyclosporine usually by inhibition or induction of CYP3A4 or P-glycoprotein transporter or both. Compounds that decrease cyclosporine absorption such as orlistat should be avoided. Appropriate Sandimmune® (cyclosporine) dosage adjustment to achieve the desired cyclosporine concentrations is essential when drugs that significantly alter cyclosporine concentrations are used concomitantly. (See Blood Concentration Monitoring.)

Drugs That Increase Cyclosporine Concentrations

 

View Enlarged Table
HIV Protease inhibitors

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 cyclosporine, however no formal studies of the interaction are available. Care should be exercised when these drugs are administered concomitantly.

Grapefruit juice

Grapefruit and grapefruit juice affect metabolism, increasing blood concentrations of cyclosporine, thus should be avoided.

Drugs/Dietary Supplements That Decrease Cyclosporine Concentrations

 

Antibiotics Anticonvulsants Other Drugs / Dietary Supplements
nafcillin
rifampin
carbamazepine oxcarbazepine phenobarbital phenytoin bosentan
octreotide
orlistat
sulfinpyrazone
terbinafine
ticlopidine
St. John’s Wort
Bosentan

Co-administration of bosentan (250 - 1000 mg every 12 hours based on tolerability) and cyclosporine (300 mg every 12 hours for 2 days then dosing to achieve a Cmin of 200-250 ng/mL) for 7 days in healthy subjects resulted in decreases in the cyclosporine mean dose-normalized AUC, Cmax, and trough concentration of approximately 50%, 30% and 60%, respectively, compared to when cyclosporine was given alone. (See also Effect of Cyclosporine on the Pharmacokinetics and/or Safety of Other Drugs or Agents)

Boceprevir

Co-administration of boceprevir (800 mg three times daily for 7 days) and cyclosporine (100 mg single dose) in healthy subjects resulted in increases in the mean AUC and Cmax of cyclosporine approximately 2.7-fold and 2-fold, respectively, compared to when cyclosporine was given alone.

Telaprevir

Co-administration of telaprevir (750 mg every 8 hours for 11 days) with cyclosporine (10 mg on day 8) in healthy subjects resulted in increases in the mean dose-normalized AUC and Cmax of cyclosporine approximately 4.5-fold and 1.3-fold, respectively, compared to when cyclosporine (100 mg single dose) was given alone.

St John's Wort

There have been reports of a serious drug interaction between cyclosporine and the herbal dietary supplement, St. John's Wort. This interaction has been reported to produce a marked reduction in the blood concentrations of cyclosporine, resulting in subtherapeutic levels, rejection of transplanted organs, and graft loss.

Rifabutin

Rifabutin is known to increase the metabolism of other drugs metabolized by the cytochrome P-450 system. The interaction between rifabutin and cyclosporine has not been studied. Care should be exercised when these two drugs are administered concomitantly.

Effect of Cyclosporine on the Pharmacokinetics and/or Safety of Other Drugs or Agents

Cyclosporine is an inhibitor of CYP3A4 and of the multidrug efflux transporter P-glycoprotein and may increase plasma concentrations of comedications that are substrates of CYP3A4 or P-glycoprotein or both.

Cyclosporine may reduce the clearance of digoxin, colchicine, prednisolone, HMG-CoA reductase inhibitors (statins) and aliskiren, repaglinide, NSAIDs, sirolimus, etoposide, and other drugs. See the full prescribing information of the other drug for further information and specific recommendations. The decision on co-administration of cyclosporine with other drugs or agents should be made by the physician following the careful assessment of benefits and risks.

Digoxin

Severe digitalis toxicity has been seen within days of starting cyclosporine in several patients taking digoxin. If digoxin is used concurrently with cyclosporine, serum digoxin concentrations should be monitored.

Colchicine

There are reports on the potential of cyclosporine to enhance the toxic effects of colchicine such as myopathy and neuropathy, especially in patients with renal dysfunction. Concomitant administration of cyclosporine and colchicine results in significant increases in colchicine plasma concentrations. If colchicine is used concurrently with cyclosporine, a reduction in the dosage of colchicine is recommended.

HMG Co-A reductase inhibitors (statins)

Literature and postmarketing cases of myotoxicity, including muscle pain and weakness, myositis, and rhabdomyolysis, have been reported with concomitant administration of cyclosporine with lovastatin, simvastatin, atorvastatin, pravastatin, and rarely, fluvastatin. When concurrently administered with cyclosporine, the dosage of these statins should be reduced according to label recommendations. Statin therapy needs to be temporarily withheld or discontinued in patients with signs and symptoms of myopathy or those with risk factors predisposing to severe renal injury, including renal failure, secondary to rhabdomyolysis.

Repaglinide

Cyclosporine may increase the plasma concentrations of repaglinide and thereby increase the risk of hypoglycemia. In 12 healthy male subjects who received two doses of 100mg cyclosporine capsule orally 12 hours apart with a single dose of 0.25mg repaglinide tablet (one half of a 0.5mg tablet) orally 13 hours after the cyclosporine initial dose, the repaglinide mean Cmax and AUC were increased 1.8 fold (range: 0.6 - 3.7 fold) and 2.4 fold (range 1.2 - 5.3 fold), respectively. Close monitoring of blood glucose level is advisable for a patient taking cyclosporine and repaglinide concomitantly.

Ambrisentan

Co-administration of ambrisentan (5 mg daily) and cyclosporine (100-150 mg twice daily initially, then dosing to achieve Cmin 150-200 ng/mL) for 8 days in healthy subjects resulted mean increases in ambrisentan AUC and Cmax of approximately 2-fold and 1.5-fold, respectively, compared to ambrisentan alone.

Anthracycline antibiotics

High doses of cyclosporine (e.g., at starting intravenous dose of 16 mg/kg/day) may increase the exposure to anthracycline antibiotics (e.g., doxorubicin, mitoxantrone, daunorubicin) in cancer patients.

Aliskiren

Cyclosporine alters the pharmacokinetics of aliskiren, a substrate of P-glycoprotein and CYP3A4. In 14 healthy subjects who received concomitantly single doses of cyclosporine (200 mg) and reduced dose aliskiren (75 mg), the mean Cmax of aliskiren was increased by approximately 2.5 fold (90% CI: 1.96 - 3.17) and the mean AUC by approximately 4.3 fold (90% CI: 3.52 - 5.21), compared to when these subjects received aliskiren alone. The concomitant administration of aliskiren with cyclosporine prolonged the median aliskiren elimination half-life (26 hours versus 43 to 45 hours) and the Tmax (0.5 hours versus 1.5 to 2.0 hours). The mean AUC and Cmax of cyclosporine were comparable to reported literature values. Co-administration of cyclosporine and aliskiren in these subjects also resulted in an increase in the number and/or intensity of adverse events, mainly headache, hot flush, nausea, vomiting, and somnolence. The co-administration of cyclosporine with aliskiren is not recommended.

Bosentan

In healthy subjects, co-administration of bosentan and cyclosporine resulted in mean increases in dose-normalized bosentan trough concentrations on day 1 and day 8 of approximately 21-fold and 2fold , respectively, compared to when bosentan was given alone as a single dose on day 1. (See also Effect of Drugs and Other Agents on Cyclosporine Pharmacokinetics and/or Safety)

Potassium sparing diuretics

Cyclosporine should not be used with potassium-sparing diuretics because hyperkalemia can occur. Caution is also required when cyclosporine is coadministered with potassium-sparing drugs (e.g., angiotensin-converting enzyme inhibitors, angiotensin II receptor antagonists), potassium-containing drugs as well as in patients on a potassium-rich diet. Control of potassium levels in these situations is advisable.

Nonsteroidal Anti-inflammatory Drug (NSAID) Interactions

Clinical status and serum creatinine should be closely monitored when cyclosporine is used with nonsteroidal anti-inflammatory agents in rheumatoid arthritis patients. (See WARNINGS)

Pharmacodynamic interactions have been reported to occur between cyclosporine and both naproxen and sulindac, in that concomitant use is associated with additive decreases in renal function, as determined by 99mTc-diethylenetriaminepentaacetic acid (DTPA) and (p-aminohippuric acid) PAH clearances. Although concomitant administration of diclofenac does not affect blood concentrations of cyclosporine, it has been associated with approximate doubling of diclofenac blood levels and occasional reports of reversible decreases in renal function. Consequently, the dose of diclofenac should be in the lower end of the therapeutic range.

Methotrexate Interaction

Preliminary data indicate that when methotrexate and cyclosporine were coadministered to rheumatoid arthritis patients (N=20), methotrexate concentrations (AUCs) were increased approximately 30% and the concentrations (AUCs) of its metabolite, 7-hydroxy methotrexate, were decreased by approximately 80%. The clinical significance of this interaction is not known. Cyclosporine concentrations do not appear to have been altered (N=6).

Sirolimus

Elevations in serum creatinine were observed in studies using sirolimus in combination with full-dose cyclosporine. This effect is often reversible with cyclosporine dose reduction. Simultaneous coadministration of cyclosporine significantly increases blood levels of sirolimus. To minimize increases in sirolimus blood concentrations, it is recommended that sirolimus be given 4 hours after cyclosporine administration.

Nifedipine

Frequent gingival hyperplasia when nifedipine is given concurrently with cyclosporine has been reported. The concomitant use of nifedipine should be avoided in patients in whom gingival hyperplasia develops as a side effect of cyclosporine.

Methylprednisolone

Convulsions when high dose methylprednisolone is given concomitantly with cyclosporine have been reported.

Other Immunosuppressive Drugs and Agents

Psoriasis patients receiving other immunosuppressive agents or radiation therapy (including PUVA and UVB) should not receive concurrent cyclosporine because of the possibility of excessive immunosuppression.

C. Effect of Cyclosporine on the Efficacy of Live Vaccines

During treatment with cyclosporine, vaccination may be less effective. The use of live vaccines should be avoided.

For additional information on Cyclosporine Drug Interactions please contact Novartis Medical Affairs Department at 888-NOW-NOVA (888-669-6682).

Read the Sandimmune Drug Interactions Center for a complete guide to possible interactions

Learn More »

This monograph has been modified to include the generic and brand name in many instances.

Warnings

Kidney, Liver and Heart Transplant

(See BOXED WARNINGS): 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 2-3 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 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.

 

View Enlarged Table

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 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 co-administering 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 comorbidities, 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 I.V. 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 breast feeding 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.

Precautions

General

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.

Laboratory Tests

Renal and liver functions should be assessed repeatedly by measurement of BUN, serum creatinine, serum bilirubin, and liver enzymes.

Carcinogenesis, Mutagenesis, and Impairment of Fertility

Cyclosporine gave no evidence of mutagenic or teratogenic effects in appropriate test systems. Only at dose levels toxic to dams, were adverse effects seen in reproduction studies in rats. (See Pregnancy.)

Carcinogenicity studies were carried out in male and female rats and mice. In the 78-week mouse study, at doses of 1, 4, and 16 mg/kg/day, evidence of a statistically significant trend was found for lymphocytic lymphomas in females, and the incidence of hepatocellular carcinomas in mid-dose males significantly exceeded the control value. In the 24-month rat study, conducted at 0.5, 2, and 8 mg/kg/day, pancreatic islet cell adenomas significantly exceeded the control rate in the low-dose level. The hepatocellular carcinomas and pancreatic islet cell adenomas were not dose related.

No impairment in fertility was demonstrated in studies in male and female rats.

Cyclosporine has not been found mutagenic/genotoxic in the Ames Test, the V79-HGPRT Test, the micronucleus test in mice and Chinese hamsters, the chromosome-aberration tests in Chinese hamster bone marrow, the mouse dominant lethal assay, and the DNA-repair test in sperm from treated mice. A recent study analyzing sister chromatid exchange (SCE) induction by cyclosporine using human lymphocytes in vitro gave indication of a positive effect (i.e., induction of SCE), at high concentrations in this system. In two published research studies, rabbits exposed to cyclosporine in utero (10 mg/kg/day subcutaneously) demonstrated reduced numbers of nephrons, renal hypertrophy, systemic hypertension and progressive renal insufficiency up to 35 weeks of age. Pregnant rats which received 12 mg/kg/day of cyclosporine intravenously (twice the recommended human intravenous dose) had fetuses with an increased incidence of ventricular septal defect. These findings have not been demonstrated in other species and their relevance for humans is unknown.

An increased incidence of malignancy is a recognized complication of immunosuppression in recipients of organ transplants. The most common forms of neoplasms are non-Hodgkin's lymphoma and carcinomas of the skin. The risk of malignancies in cyclosporine recipients is higher than in the normal, healthy population, but similar to that in patients receiving other immunosuppressive therapies. It has been reported that reduction or discontinuance of immunosuppression may cause the lesions to regress.

Pregnancy

Pregnancy Category C

Animal studies have shown reproductive toxicity in rats and rabbits. Cyclosporine gave no evidence of mutagenic or teratogenic effects in the standard test systems with oral application (rats up to 17 mg/kg and rabbits up to 30 mg/kg per day orally). Sandimmune® Oral Solution (cyclosporine oral solution, USP) has been shown to be embryo- and fetotoxic in rats and rabbits when given in doses 2-5 times the human dose. At toxic doses (rats at 30 mg/kg/day and rabbits at 100 mg/kg/day), Sandimmune® Oral Solution (cyclosporine oral solution, USP) was embryo- and fetotoxic as indicated by increased pre- and postnatal mortality and reduced fetal weight together with related skeletal retardations. In the well-tolerated dose range (rats at up to 17 mg/kg/day and rabbits at up to 30 mg/kg/day), Sandimmune® Oral Solution (cyclosporine oral solution, USP) proved to be without any embryolethal or teratogenic effects.

There are no adequate and well-controlled studies in pregnant women and therefore, Sandimmune® (cyclosporine) should not be used during pregnancy unless the potential benefit to the mother justifies the potential risk to the fetus.

In pregnant transplant recipients who are being treated with immunosuppressants, the risk of premature birth is increased. The following data represent the reported outcomes of 116 pregnancies in women receiving Sandimmune® (cyclosporine) during pregnancy, 90% of whom were transplant patients, and most of whom received Sandimmune® (cyclosporine) throughout the entire gestational period. Since most of the patients were not prospectively identified, the results are likely to be biased toward negative outcomes. The only consistent patterns of abnormality were premature birth (gestational period of 28 to 36 weeks) and low birth weight for gestational age. It is not possible to separate the effects of Sandimmune® (cyclosporine) on these pregnancies from the effects of the other immunosuppressants, the underlying maternal disorders, or other aspects of the transplantation milieu. Sixteen fetal losses occurred. Most of the pregnancies (85 of 100) were complicated by disorders; including, preeclampsia, eclampsia, premature labor, abruptio placentae, oligohydramnios, Rh incompatibility and fetoplacental dysfunction. Preterm delivery occurred in 47%. Seven malformations were reported in 5 viable infants and in 2 cases of fetal loss. Twenty-eight percent of the infants were small for gestational age. Neonatal complications occurred in 27%. In a report of 23 children followed up to 4 years, postnatal development was said to be normal. More information on cyclosporine use in pregnancy is available from Novartis Pharmaceuticals Corporation.

A limited number of observations in children exposed to cyclosporine in utero are available, up to an age of approximately 7 years. Renal function and blood pressure in these children were normal.

The alcohol content of the Sandimmune formulations should also be taken into account in pregnant women. (See WARNINGS, Special Excipients)

Nursing Mothers

Cyclosporine is present in breast milk. Because of the potential for serious adverse drug reactions in nursing infants from Sandimmune, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. Sandimmune contains ethanol. Ethanol will be present in human milk at levels similar to that found in maternal serum and if present in breast milk will be orally absorbed by a nursing infant. (See WARNINGS)

Pediatric Use

Although no adequate and well-controlled studies have been conducted in children, patients as young as 6 months of age have received the drug with no unusual adverse effects.

Geriatric Use

Clinical studies of Sandimmune® (cyclosporine) did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger patients. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

This monograph has been modified to include the generic and brand name in many instances.

OverDose

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 LD50 is 2329 mg/kg in mice, 1480 mg/kg in rats, and > 1000 mg/kg in rabbits. The I.V. LD50 is 148 mg/kg in mice, 104 mg/kg in rats, and 46 mg/kg in rabbits.

ContrainDications

Sandimmune® Injection (cyclosporine injection, USP) is contraindicated in patients with a hypersensitivity to Sandimmune® (cyclosporine) and/or Cremophor® EL (polyoxyethylated castor oil).

This monograph has been modified to include the generic and brand name in many instances.

Clinical Pharamacology

Sandimmune® (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. Sandimmune® (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 Sandimmune® (cyclosporine).

The exact mechanism of action of Sandimmune® (cyclosporine) is not known. Experimental evidence suggests that the effectiveness of cyclosporine is due to specific and reversible inhibition of immunocompetent lymphocytes in the G0- or G1-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. Sandimmune® (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 in vivo) or tumor cells (growth rate, metastasis) can be detected in animals. Sandimmune® (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 (Cmax) in blood and plasma are achieved at about 3.5 hours. Cmax 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, Cmax is approximately 1.0 ng/mL/mg of dose for plasma and 2.7-1.4 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%-47% is in plasma, 4%-9% in lymphocytes, 5%-12% in granulocytes, and 41%-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: 10-27 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-N,4-dimethyl-L-2-amino-6-octenoic acid and Ndemethylation of N-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 < 5 mL/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.

This monograph has been modified to include the generic and brand name in many instances.

Patient Information

Patients should be advised that any change of cyclosporine formulation should be made cautiously and only under physician supervision because it may result in the need for a change in dosage.

Patients should be informed of the necessity of repeated laboratory tests while they are receiving the drug. They should be given careful dosage instructions, advised of the potential risks during pregnancy, and informed of the increased risk of neoplasia.

Patients using cyclosporine oral solution with its accompanying syringe for dosage measurement should be cautioned not to rinse the syringe either before or after use. Introduction of water into the product by any means will cause variation in dose.

This monograph has been modified to include the generic and brand name in many instances.

Consumer Overview Uses

IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.

 

CYCLOSPORINE SOLUTION - ORAL

 

(sye-klo-SPORE-een)

 

COMMON BRAND NAME(S): Sandimmune

 

WARNING: Cyclosporine is a drug that reduces the body's ability to fight illness/disease (an immunosuppressant), leaving patients vulnerable to infection or other problems (including cancers such as lymphoma). Using other drugs that treat organ transplant rejection along with this drug may increase these tendencies.

Cyclosporine can also cause high blood pressure and kidney problems. The risk of both problems increases with higher doses and longer treatment with this drug. Psoriasis patients who have had certain previous treatments (e.g., PUVA, UVB, coal tar, radiation therapy, methotrexate) are at increased risk to develop skin cancer. Therefore, cyclosporine must be given only under close medical supervision.

Because different brands deliver different amounts of medication, do not switch brands of cyclosporine without your doctor's permission and directions.

Laboratory tests (e.g., kidney function tests, blood tests) may be performed to monitor your progress.

 

USES: This medication is used to prevent organ rejection in people who have received a liver, kidney, or heart transplant. It is usually taken along with other medications to allow your new organ to function normally. Cyclosporine is also used to treat severe rheumatoid arthritis and a certain skin condition (severe psoriasis). Cyclosporine belongs to a class of drugs known as immunosuppressants. It works by slowing down your body's defense system (immune system) to prevent your body from rejecting a transplanted organ, further damaging your joints (in rheumatoid arthritis patients), or further damaging your skin (in psoriasis patients). For the treatment of psoriasis or arthritis, it is generally used to treat people who cannot take other medications or have not found relief from other treatments.

 

OTHER USES: This section contains uses of this drug that are not listed in the approved professional labeling for the drug but that may be prescribed by your health care professional. Use this drug for a condition that is listed in this section only if it has been so prescribed by your health care professional.

This drug may also be used to prevent rejection in other types of organ transplants (e.g., cornea, pancreas) or bone marrow transplant. It may also be used to treat other conditions that may be helped by affecting the immune system (e.g., Crohn's disease).

 

HOW TO USE: Take this medication by mouth, usually once daily at the same time each day, or take as directed by your doctor. You may take it with or without food, but it is important to choose one way and take every dose that way. Dosage is based on your medical condition, cyclosporine blood level, kidney function, and response to therapy. Follow the dosing schedule for this medication carefully.

To improve the taste of this liquid medication, mix it with milk, chocolate milk, or orange juice. Using the dosing syringe, measure your dose into a cup of milk or orange juice, stir well, and drink as soon as possible. It is best to use a glass cup whenever possible, but a hard plastic cup may also be used. Do not use plastic foam cups. To make sure that all the medication is taken, add more juice to the cup, stir, and drink, then repeat. Dry the outside of the dropper. Do not rinse it in water.

Avoid eating grapefruit or drinking grapefruit juice while being treated with this medication unless your doctor instructs you otherwise. Grapefruit products can increase the amount of this medication in your bloodstream. Consult your doctor or pharmacist for more details.

Use this medication regularly in order to get the most benefit from it. Remember to use it at the same time each day.

This medication works best when the amount of medicine in your body is kept at a constant level. Therefore, take this drug at evenly spaced intervals.

If you are taking this drug to treat arthritis, it may take 4-8 weeks to notice improvement, and up to 4 months for the full benefit.

If you are taking this drug to treat psoriasis, it may take 2-4 weeks to notice improvement, and up to 4 months for the full benefit. Your dose will slowly be increased during your therapy with this drug. Inform your doctor if your condition does not improve after 6 weeks of taking the highest recommended dose. If you are taking this medication to treat psoriasis, do not take it continuously for longer than one year unless directed to do so by your doctor.

Consumer Overview Side Effect

SIDE EFFECTS: See also the Warning section.

Headache, nausea, vomiting, diarrhea, stomach upset, acne, cramps, increased hair growth on the face/body, shaking fingers/hands (tremor), swollen/red/painful gums, dizziness, flushing, and high blood pressure may occur. If any of these effects persist or worsen, notify your doctor or pharmacist promptly.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Your risk of infection may be higher while you are taking this medication. Tell your doctor immediately if any of these symptoms of infection occur: fever, sore throat, flu-like symptoms, painful urination.

Tell your doctor right away if you have any serious side effects, including: muscle spasms/weakness, fast/irregular heartbeat, change in the amount/color of urine, unusual weight gain/loss, tingling of the hands/feet, hearing problems, easy bruising/bleeding, unusual tiredness, dark urine, persistent nausea/vomiting, severe stomach/abdominal pain, yellowing of the skin/eyes, vomit that looks like coffee grounds, change in the appearance or size of skin moles/lesions, changes in skin color, loss of consciousness, mental/mood changes (such as confusion, difficulty concentrating), vision changes, swollen glands, unusual lumps, night sweats, problems with speech, clumsiness, loss of coordination, weakness on one side of the body.

Get medical help right away if you have any very serious side effects, including: chest pain, seizures.

A very serious allergic reaction to this drug is unlikely, but seek immediate medical attention if it occurs. Symptoms of a serious allergic reaction include: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

In the US -

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

 

Read the Sandimmune (cyclosporine) Side Effects Center for a complete guide to possible side effects

Learn More »

PRECAUTIONS: Before taking cyclosporine, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

This medication should not be used if you have certain medical conditions. Before using this medicine, consult your doctor or pharmacist if you have: history of chicken pox/shingles, uncontrolled high blood pressure, cancer, skin lesions of unknown cause, current use of radiation therapy (including phototherapy with PUVA or UVB), kidney problems (for arthritis or psoriasis patients only).

Before using this medication, tell your doctor or pharmacist your medical history, especially of: kidney disease, liver disease, any recent/current infections, seizures, untreated mineral imbalance (e.g., low magnesium or high potassium), blood disorders, diabetes, a certain gut problem (malabsorption), high blood fats (cholesterol or triglycerides).

This drug may make you dizzy. Do not drive, use machinery, or do any activity that requires alertness until you are sure you can perform such activities safely. Limit alcoholic beverages.

This drug may reduce the magnesium levels in your blood. Ask your doctor about adding magnesium to your diet. Your doctor may prescribe a magnesium supplement.

Cyclosporine can make you more likely to get infections or may worsen any current infections. Therefore, wash your hands well to prevent the spread of infection. Avoid contact with people who have infections that may spread to others (such as chickenpox, measles, flu). Consult your doctor if you have been exposed to an infection or for more details.

Do not have immunizations/vaccinations without the consent of your doctor. Avoid contact with people who have recently received live vaccines (such as flu vaccine inhaled through the nose).

This drug may increase your risk for developing skin cancer. Avoid prolonged sun exposure, tanning booths and sunlamps. Use a sunscreen and wear protective clothing when outdoors.

This medication may cause swelling and growth of the gums (gingival hyperplasia). Brush your teeth and floss daily to minimize this problem. See your dentist regularly.

This medication may contain alcohol. Caution is advised if you have liver disease, alcohol dependence, seizures, or any other condition that require you to limit/avoid alcohol in your diet. Caution is also advised if you are pregnant or breast-feeding. Carefully watch children while they use this medication. Ask your doctor or pharmacist about using this product safely.

Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).

The elderly may be at greater risk for the effects on blood pressure and kidneys while using this drug.

This medication should be used only when clearly needed during pregnancy. Cyclosporine used during pregnancy has resulted in newborns with problems such as low birth weight and being born too early (premature). Other more serious problems have also been reported, including death of the unborn baby. Discuss the risks and benefits with your doctor.

This medication passes into breast milk. Because of the possible risk to the infant, breast-feeding while using this drug is not recommended. Consult your doctor before breast-feeding.

Consumer Overview Missed Dose

DRUG INTERACTIONS: See also the How to Use section.

Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor's approval.

Some products that may interact with this drug include: birth control pills, caspofungin, coal tar, ezetimibe, sulfinpyrazone, tacrolimus, temsirolimus, terbinafine, other drugs that weaken the immune system/increase the risk of infection (such as natalizumab, rituximab, tofacitinib), drugs that worsen kidney problems (e.g., acyclovir, aminoglycoside antibiotics including tobramycin; amphotericin B; colchicine; fibrates including fenofibrate; melphalan; NSAIDs including diclofenac and sulindac; ranitidine; sulfa drugs including sulfamethoxazole; vancomycin), drugs that may increase potassium levels (e.g., ACE inhibitors including lisinopril, ARBs including losartan, potassium supplements, "water pills" including amiloride, spironolactone).

Other medications can affect the removal of cyclosporine from your body, which may affect how cyclosporine works. Examples include allopurinol, amiodarone, azole antifungals including fluconazole, barbiturates including phenobarbital, boceprevir, bosentan, bromocriptine, calcium channel blockers including diltiazem/nifedipine/verapamil, cimetidine, HIV protease inhibitors including indinavir, imatinib, certain man-made male hormones such as danazol/methyltestosterone, methylprednisolone, metoclopramide, metronidazole, mifepristone, nafcillin, nefazodone, octreotide, orlistat, quinupristin/dalfopristin, rifamycins including rifampin/rifabutin, certain anti-seizure drugs including carbamazepine/phenytoin, St. John's wort, telaprevir, ticlopidine, among others.

This medication can slow down the removal of other medications from your body, which may affect how they work. Examples of affected drugs include aliskiren, ambrisentan, digoxin, dronedarone, etoposide, repaglinide, tolterodine, statins (such as atorvastatin, lovastatin, pitavastatin, rosuvastatin, simvastatin), other immunosuppressants (such as azathioprine, methotrexate, sirolimus), among others.

Do not use potassium-containing salt substitutes while taking this medication. Consult your doctor or pharmacist for more information.

 

OVERDOSE: If overdose is suspected, contact a poison control center or emergency room immediately. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center.

 

NOTES: Do not share this medication with others.

Keep all laboratory and medical appointments. Laboratory and/or medical tests (e.g., liver and kidney function, blood pressure, blood mineral levels, uric acid, cyclosporine blood levels) should be performed from time to time to monitor your progress or check for side effects. Consult your doctor for more details.

Have your blood pressure checked regularly while taking this medication. Discuss with your doctor how to monitor your own blood pressure. Inform your doctor of your blood pressure readings.

If you have had an organ transplant, it is recommended that you attend a transplant education class or support group. Learn the symptoms of organ rejection such as a feeling of being ill, fever, pain around the transplanted organ, and signs of a failing transplanted organ (a decrease in the amount of urine with kidney transplant, yellowing of the skin/eyes with liver transplant, shortness of breath/inability to exercise with heart transplant). Seek immediate medical attention if these symptoms of rejection occur.

 

MISSED DOSE: If you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

 

STORAGE: Store in the original container at room temperature below 86 degrees F (30 degrees C). Do not refrigerate or freeze. Once the bottle is opened, use the solution within 2 months. Do not store in the bathroom. Keep all medicines away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

 

MEDICAL ALERT: Your condition can cause complications in a medical emergency. For information about enrolling in MedicAlert, call 1-888-633-4298 (US) or 1-800-668-1507 (Canada).

 

Information last revised July 2013. Copyright(c) 2013 First Databank, Inc.

Patient Detailed Side Effect

Brand Names: Gengraf, Neoral, Sandimmune

Generic Name: cyclosporine (Pronunciation: SYE kloe SPOR een)

  • What is cyclosporine (Sandimmune)?
  • What are the possible side effects of cyclosporine (Sandimmune)?
  • What is the most important information I should know about cyclosporine (Sandimmune)?
  • What should I discuss with my health care provider before taking cyclosporine (Sandimmune)?
  • How should I take cyclosporine (Sandimmune)?
  • What happens if I miss a dose (Sandimmune)?
  • What happens if I overdose (Sandimmune)?
  • What should I avoid while taking cyclosporine (Sandimmune)?
  • What other drugs will affect cyclosporine (Sandimmune)?
  • Where can I get more information?

What is cyclosporine (Sandimmune)?

Cyclosporine lowers your body's immune system. The immune system helps your body fight infections. The immune system can also fight or "reject" a transplanted organ such as a liver or kidney. This is because the immune system treats the new organ as an invader.

Cyclosporine is used to prevent organ rejection after a kidney, heart, or liver transplant. Cyclosporine is also used to treat severe psoriasis or severe rheumatoid arthritis.

Cyclosporine may also be used for purposes not listed in this medication guide.

Cyclosporine 100 mg-APO

capsule, brown, imprinted with APO 134, 100

What are the possible side effects of cyclosporine (Sandimmune)?

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have a serious side effect such as:

  • fever, sweating, chills, body aches, flu symptoms, sores in your mouth and throat, weight loss;
  • change in your mental state, problems with speech or walking, decreased vision (may start gradually and get worse quickly);
  • easy bruising or bleeding, pale skin, confusion or weakness;
  • feeling light-headed or short of breath, rapid heart rate, trouble concentrating;
  • pain in the lower back or side, blood in your urine, pain or burning when you urinate;
  • urinating less than usual or not at all, rapid weight gain;
  • swelling, warmth, redness, or oozing of the skin;
  • vomiting and bloody diarrhea;
  • seizure (convulsions);
  • high potassium (slow heart rate, weak pulse, muscle weakness, tingly feeling);
  • nausea, upper stomach pain, itching, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes); or
  • dangerously high blood pressure (severe headache, blurred vision, buzzing in your ears, anxiety, chest pain, shortness of breath, uneven heartbeats).

Less serious side effects may include:

  • swollen or painful gums;
  • mild headache;
  • stomach pain, constipation, mild diarrhea; or
  • tremors or shaking, muscle spasm, numbness or tingly feeling.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the Sandimmune (cyclosporine) Side Effects Center for a complete guide to possible side effects

Learn More »

What is the most important information I should know about cyclosporine (Sandimmune)?

Cyclosporine may increase your risk of developing serious infections, cancer, or transplant failure. Talk with your doctor about the risks and benefits of using this medication.

You may not be able to use this medication if you have kidney disease, untreated or uncontrolled hypertension (high blood pressure), any type of cancer, or psoriasis that has been treated with PUVA, UVB, radiation, methotrexate (Trexall), or coal tar. MAKE SURE ALL DOCTORS INVOLVED IN YOUR CARE KNOW YOU ARE TAKING CYCLOSPORINE.

You will need regular medical tests to be sure cyclosporine is not causing harmful effects. Do not miss any follow up visits to your doctor for blood or urine tests. Avoid being near people who are sick or have infections.

Cyclosporine can harm your kidneys, and this effect is increased when you also use certain other medicines harmful to the kidneys. Many other drugs (including some over-the-counter medicines) can be harmful to the kidneys.

Cyclosporine can cause serious side effects, including kidney failure or life-threatening infection. Call your doctor at once if you have any signs of kidney failure (urinating less than usual or not at all, swelling, rapid weight gain, feeling short of breath) or signs of infection (fever, sweating, chills, tired feeling, cough, sores in your mouth and throat, flu symptoms, weight loss).

Call your doctor right away if you have symptoms of a serious brain infection, such as a change in your mental state, problems with speech or walking, or decreased vision. These symptoms may start gradually and get worse quickly.

Side Effects Centers
  • Sandimmune
  • Neoral
  • Gengraf Oral Solution
  • Gengraf Capsules

Patient Detailed How Take

What should I discuss with my health care provider before taking cyclosporine (Sandimmune)?

You should not use this medication if you are allergic to cyclosporine. You may not be able to use cyclosporine if you have:

  • kidney disease;
  • untreated or uncontrolled high blood pressure; or
  • any type of cancer.

If you are being treated for psoriasis, you should not receive ultraviolet light therapy (PUVA or UVB), radiation treatments, coal tar, or drugs that weaken the immune system (such as methotrexate) while you are receiving cyclosporine.

MAKE SURE ALL DOCTORS INVOLVED IN YOUR CARE KNOW YOU ARE TAKING CYCLOSPORINE.

Cyclosporine can lower blood cells that help your body fight infections, or cause your body to produce too much of a certain type of white blood cells. This can lead to serious and sometimes fatal conditions, including cancer, a severe brain infection that can lead to disability or death, or a virus that can cause failure of a transplanted kidney. Talk with your doctor about your specific risk.

FDA pregnancy category C. It is not known whether cyclosporine will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant while using this medication.

Cyclosporine can pass into breast milk and may harm a nursing baby. You should not breast-feed while you are using cyclosporine.

How should I take cyclosporine (Sandimmune)?

Take exactly as prescribed by your doctor. Do not take in larger or smaller amounts or for longer than recommended. Follow the directions on your prescription label. Your doctor may occasionally change your dose to make sure you get the best results.

You may take cyclosporine with or without food, but take it the same way each time. Cyclosporine should be given in two separate doses each day. Try to take the medication at the same dosing times each day.

If your doctor changes your brand, strength, or type of cyclosporine, your dosage needs may change. Ask your pharmacist if you have any questions about the new kind of cyclosporine you receive at the pharmacy.

Measure liquid medicine with a special dose-measuring spoon or cup, not a regular table spoon. If you do not have a dose-measuring device, ask your pharmacist for one. Sandimmune oral solution may be mixed with milk, chocolate milk, or orange juice at room temperature to make the medicine taste better. Neoral "modified" (microemulsion) oral solution should be mixed with orange juice or apple juice that is at room temperature.

You will need regular medical tests to be sure this medication is not causing harmful effects. Visit your doctor regularly. Do not miss any follow up visits to your doctor for blood or urine tests.

Your condition may need to be treated with a combination of different drugs. Use all medications as directed by your doctor. Read the medication guide or patient instructions provided with each medication. Do not change your doses or medication schedule without your doctor's advice. Every person taking cyclosporine should remain under the care of a doctor.

Store at room temperature away from moisture and heat.

Side Effects Centers
  • Sandimmune
  • Neoral
  • Gengraf Oral Solution
  • Gengraf Capsules

Patient Detailed Avoid Taking

What happens if I miss a dose (Sandimmune)?

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

What happens if I overdose (Sandimmune)?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Overdose can cause nausea, vomiting, pain in your upper stomach, loss of appetite, jaundice (yellowing of the skin or eyes), and urinating less than usual or not at all.

What should I avoid while taking cyclosporine (Sandimmune)?

Avoid being near people who are sick or have infections. Tell your doctor at once if you develop signs of infection.

Grapefruit and grapefruit juice may interact with cyclosporine and lead to unwanted side effects. Discuss the use of grapefruit products with your doctor.

Avoid exposure to sunlight or tanning beds. Cyclosporine can make you sunburn more easily. Wear protective clothing and use sunscreen (SPF 30 or higher) when you are outdoors.

Do not receive a "live" vaccine while using cyclosporine. The vaccine may not work as well during this time, and may not fully protect you from disease. Live vaccines include measles, mumps, rubella (MMR), Bacillus Calmette-Guérin (BCG), oral polio, rotavirus, smallpox, typhoid, yellow fever, varicella (chickenpox), zoster (shingles), and nasal flu (influenza) vaccine.

What other drugs will affect cyclosporine (Sandimmune)?

Cyclosporine can harm your kidneys. This effect is increased when you also use other medicines harmful to the kidneys. Many other drugs (including some over the counter medicines) can be harmful to the kidneys. You may need dose adjustments or special tests if you have recently used:

  • an antibiotic or antifungal medication;
  • cancer medication;
  • cholesterol-lowering drugs;
  • gout medication;
  • medicines to treat psoriasis, rheumatoid arthritis, or other autoimmune disorders;
  • an NSAID (non-steroidal anti-inflammatory drug) such as ibuprofen (Advil, Motrin), naproxen (Aleve, Naprosyn, Naprelan, Treximet), celecoxib (Celebrex), diclofenac (Arthrotec, Cambia, Cataflam, Voltaren, Flector Patch, Pennsaid, Solareze), indomethacin (Indocin), meloxicam (Mobic), and others;
  • other medicines used to prevent organ transplant rejection; or
  • stomach acid reducers (Tagamet, Zantac).

Many other drugs can interact with cyclosporine. Below is just a partial list. Tell your doctor about all other medications you are using, especially:

  • birth control pills;
  • a diuretic (water pill);
  • gout medication;
  • heart or blood pressure medication;
  • HIV or AIDS medication;
  • seizure medication;
  • steroid medication (oral, nasal, inhaled, or injectable); or
  • St. John's wort.

This list is not complete and there are many other drugs that can interact with cyclosporine. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor. Keep a list of all your medicines and show it to any healthcare provider who treats you.

Where can I get more information?

Your pharmacist can provide more information about cyclosporine.


Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

Every effort has been made to ensure that the information provided by Cerner Multum, Inc. ('Multum') is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. Multum information has been compiled for use by healthcare practitioners and consumers in the United States and therefore Multum does not warrant that uses outside of the United States are appropriate, unless specifically indicated otherwise. Multum's drug information does not endorse drugs, diagnose patients or recommend therapy. Multum's drug information is an informational resource designed to assist licensed healthcare practitioners in caring for their patients and/or to serve consumers viewing this service as a supplement to, and not a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient. Multum does not assume any responsibility for any aspect of healthcare administered with the aid of information Multum provides. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse or pharmacist.

Copyright 1996-2013 Cerner Multum, Inc. Version: 5.01. Revision date: 10/15/2012.

Your use of the content provided in this service indicates that you have read,understood and agree to the End-User License Agreement,which can be accessed by clicking on this link.

Healthwise

Side Effects Centers
  • Sandimmune
  • Neoral
  • Gengraf Oral Solution
  • Gengraf Capsules

Rx Scoops
Featured Topics
Advertisements
Copyrights ©2014: Rx Scoops - Designed & Developed By - GOIGI