Neoral 25mg Capsules
WARNING: You may have more of a chance of getting an infection. Some infections have been severe or deadly. Wash hands often. Stay away from people with infections, colds, or flu.Lymphoma and other cancers have happened in people who take this drug or drugs like it. This has been deadly in some cases. Talk with the doctor.If this drug is given with other drugs that work on the immune system, it can add to the chance of getting an infection or lymphoma or other cancers. Call your doctor right away if you have a change in color or size of a mole; a lump in the armpit, groin, or neck; or any new or changing skin lump or growth. Talk with the doctor.Call your doctor right away if you have any signs of infection like fever, chills, flu-like signs, very bad sore throat, ear or sinus pain, cough, more sputum or change in color of sputum, pain with passing urine, mouth sores, or a wound that will not heal.This drug may cause kidney problems in some patients. Talk with the doctor. High blood pressure has happened with this drug. Have your blood pressure checked as you have been told by your doctor.Have your blood work and other lab tests checked as you have been told by your doctor.There are different brands and forms of this drug. Do not switch between different brands or forms of this drug without calling the doctor who ordered it.If you are taking this drug for psoriasis AND you have used other drugs or radiation to treat this health problem before, your chance of skin cancer may be higher. @ COMMON USES: It is used to keep the body from harming the organ after an organ transplant.It is used to treat rheumatoid arthritis.It is used to treat psoriasis.It may be given to you for other reasons. Talk with the doctor.
Drug Class
Immunosuppressant
Pharmacologic Class
Calcineurin Inhibitor
Pregnancy Category
Category C
FDA Approved
Jan 1995
DEA Schedule
Not Controlled
Overview
What is this medicine?
Cyclosporine is a medicine that helps prevent your body from rejecting a transplanted organ (like a kidney, liver, or heart). It works by weakening your immune system so it doesn't attack the new organ. It's also used to treat severe rheumatoid arthritis and psoriasis by calming down an overactive immune system. Because it weakens your immune system, it's very important to take it exactly as prescribed and be aware of potential side effects like kidney problems, high blood pressure, and increased risk of infections.
How to Use This Medicine
Taking Your Medication Correctly
To ensure you get the most benefit from your medication, follow these guidelines:
Take your medication exactly as directed by your doctor and read all the information provided to you.
Follow the instructions carefully and take your medication at the same time every day.
You can take your medication with or without food, but be consistent in how you take it each time. For example, always take it with food or always take it on an empty stomach.
If you are also taking sirolimus, wait 4 hours after taking this medication before taking sirolimus.
Continue taking your medication as prescribed by your doctor or healthcare provider, even if you start to feel better.
Storing and Disposing of Your Medication
To maintain the quality and safety of your medication:
Store it in its original container at room temperature.
Keep it in a dry place, away from the bathroom.
Store all medications in a safe location, out of the reach of children and pets.
What to Do If You Miss a Dose
If you miss a dose, follow these steps:
Take the missed dose as soon as you remember.
If it's close to the time for your next dose, skip the missed dose and resume your regular schedule.
* Do not take two doses at the same time or take extra doses to make up for a missed one.
To ensure you get the most benefit from your medication, follow these guidelines:
Take your medication exactly as directed by your doctor and read all the information provided to you.
Follow the instructions carefully and take your medication at the same time every day.
You can take your medication with or without food, but be consistent in how you take it each time. For example, always take it with food or always take it on an empty stomach.
If you are also taking sirolimus, wait 4 hours after taking this medication before taking sirolimus.
Continue taking your medication as prescribed by your doctor or healthcare provider, even if you start to feel better.
Storing and Disposing of Your Medication
To maintain the quality and safety of your medication:
Store it in its original container at room temperature.
Keep it in a dry place, away from the bathroom.
Store all medications in a safe location, out of the reach of children and pets.
What to Do If You Miss a Dose
If you miss a dose, follow these steps:
Take the missed dose as soon as you remember.
If it's close to the time for your next dose, skip the missed dose and resume your regular schedule.
* Do not take two doses at the same time or take extra doses to make up for a missed one.
Lifestyle & Tips
- Take cyclosporine at the same time each day, consistently with or without food (but be consistent).
- Do not switch between Neoral and other cyclosporine formulations (e.g., Sandimmune, Gengraf) without your doctor's explicit instruction, as they are not interchangeable.
- Avoid grapefruit and grapefruit juice, as they can significantly increase cyclosporine levels and lead to toxicity.
- Avoid St. John's Wort, as it can significantly decrease cyclosporine levels and lead to organ rejection.
- Limit sun exposure and use sunscreen/protective clothing due to increased risk of skin cancer.
- Practice good hygiene to reduce infection risk (e.g., frequent hand washing).
- Report any signs of infection (fever, chills, sore throat) immediately.
- Avoid live vaccines while on cyclosporine.
- Monitor blood pressure regularly at home if advised by your doctor.
- Maintain a healthy diet and exercise routine as advised by your healthcare team.
Available Forms & Alternatives
Available Strengths:
Generic Alternatives:
Dosing & Administration
Adult Dosing
Standard Dose:
Highly individualized, based on indication and therapeutic drug monitoring (TDM).
Dose Range:
2 - 15 mg
Condition-Specific Dosing:
kidneyTransplantProphylaxis:
Initial: 10-15 mg/kg/day orally in two divided doses, starting 4-12 hours pre-transplant. Maintenance: 2-6 mg/kg/day.
liverTransplantProphylaxis:
Initial: 10-15 mg/kg/day orally in two divided doses, starting 4-12 hours pre-transplant. Maintenance: 2-6 mg/kg/day.
heartTransplantProphylaxis:
Initial: 10-15 mg/kg/day orally in two divided doses, starting 4-12 hours pre-transplant. Maintenance: 2-6 mg/kg/day.
rheumatoidArthritis:
Initial: 2.5 mg/kg/day orally in two divided doses. May increase by 0.5-0.75 mg/kg/day every 4 weeks to a maximum of 4 mg/kg/day.
psoriasis:
Initial: 2.5 mg/kg/day orally in two divided doses. May increase by 0.5 mg/kg/day every 2 weeks to a maximum of 5 mg/kg/day.
Pediatric Dosing
Neonatal:
Not established
Infant:
Dosing similar to adults for transplant prophylaxis, but highly individualized based on TDM and body surface area/weight.
Child:
Dosing similar to adults for transplant prophylaxis, but highly individualized based on TDM and body surface area/weight.
Adolescent:
Dosing similar to adults for transplant prophylaxis, but highly individualized based on TDM and body surface area/weight.
Dose Adjustments
Renal Impairment:
Mild:
No specific dose adjustment for mild impairment in transplant patients, but monitor cyclosporine levels and renal function closely. For non-transplant indications, consider dose reduction if SCr increases by >30% from baseline.
Moderate:
Monitor cyclosporine levels and renal function closely. Dose reduction may be necessary to maintain target trough levels and prevent further renal toxicity.
Severe:
Monitor cyclosporine levels and renal function closely. Significant dose reduction may be required. Use with extreme caution.
Dialysis:
Cyclosporine is not significantly removed by hemodialysis or peritoneal dialysis. Dose adjustment is generally not required based on dialysis status, but rather on residual renal function and TDM.
Hepatic Impairment:
Mild:
Monitor cyclosporine levels closely. Dose reduction may be necessary.
Moderate:
Significant dose reduction (e.g., 25-50% of usual dose) is typically required. Monitor cyclosporine levels closely.
Severe:
Significant dose reduction (e.g., 50-75% of usual dose) is typically required. Monitor cyclosporine levels closely. Use with extreme caution.
Pharmacology
Mechanism of Action
Cyclosporine is a calcineurin inhibitor. It forms a complex with cyclophilin, an intracellular immunophilin. This complex then binds to and inhibits calcineurin, a calcium-dependent phosphatase. Inhibition of calcineurin prevents the dephosphorylation of the nuclear factor of activated T-cells (NF-AT), which is required for its translocation into the nucleus. This, in turn, inhibits the transcription of various cytokine genes, including interleukin-2 (IL-2), IL-3, IL-4, TNF-alpha, and GM-CSF. The net effect is the inhibition of T-lymphocyte activation and proliferation, thereby suppressing the immune response.
Pharmacokinetics
Absorption:
Bioavailability:
20-50% (Neoral has more consistent and higher bioavailability than Sandimmune, approximately 30% higher AUC)
Tmax:
1.5-2 hours
FoodEffect:
Food (especially high-fat meals) can delay and decrease absorption, though the effect is less pronounced with Neoral compared to Sandimmune. Consistent administration relative to meals is recommended.
Distribution:
Vd:
3.5-5 L/kg
ProteinBinding:
90-98% (primarily to lipoproteins)
CnssPenetration:
Limited
Elimination:
HalfLife:
8-24 hours (highly variable, depends on patient population and liver function)
Clearance:
0.4-0.7 L/hr/kg
ExcretionRoute:
Primarily biliary (fecal), <6% renal
Unchanged:
<1% (in urine)
Pharmacodynamics
OnsetOfAction:
Immunosuppressive effects are observed within hours to days, but full therapeutic effect and stable trough levels may take several days to weeks.
PeakEffect:
Correlates with peak blood concentrations (Tmax), but clinical immunosuppression is related to sustained trough levels.
DurationOfAction:
Dependent on continued dosing and maintenance of therapeutic trough levels.
Safety & Warnings
BLACK BOX WARNING
Cyclosporine (MODIFIED) should be administered under the supervision of a physician experienced in immunosuppressive therapy and management of organ transplant patients. Patients receiving the drug should be managed in facilities equipped and staffed with adequate laboratory and supportive medical resources. The physician responsible for maintenance therapy should have complete information requisite for the follow-up of the patient.
Increased susceptibility to infection and the possible development of lymphoma and other malignancies are complications of immunosuppression. These risks are increased with increasing doses and duration of cyclosporine.
Neoral (cyclosporine capsules, modified) and Sandimmune (cyclosporine capsules, USP) are not bioequivalent and cannot be used interchangeably without physician supervision. For a given trough concentration, exposure (AUC) of cyclosporine will be greater with Neoral than with Sandimmune. Therefore, patients on Sandimmune should be converted to Neoral with caution.
Renal impairment, including structural kidney damage, is a common and serious side effect of cyclosporine.
Hypertension and hirsutism are also common side effects.
Increased susceptibility to infection and the possible development of lymphoma and other malignancies are complications of immunosuppression. These risks are increased with increasing doses and duration of cyclosporine.
Neoral (cyclosporine capsules, modified) and Sandimmune (cyclosporine capsules, USP) are not bioequivalent and cannot be used interchangeably without physician supervision. For a given trough concentration, exposure (AUC) of cyclosporine will be greater with Neoral than with Sandimmune. Therefore, patients on Sandimmune should be converted to Neoral with caution.
Renal impairment, including structural kidney damage, is a common and serious side effect of cyclosporine.
Hypertension and hirsutism are also common side effects.
Side Effects
Serious Side Effects: Seek Medical Help Right Away
Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you notice any of the following symptoms, contact your doctor or seek immediate medical attention:
Signs of an allergic reaction, such as:
+ Rash
+ Hives
+ Itching
+ Red, swollen, blistered, or peeling skin with or without fever
+ Wheezing
+ Tightness in the chest or throat
+ Trouble breathing, swallowing, or talking
+ Unusual hoarseness
+ Swelling of the mouth, face, lips, tongue, or throat
Signs of high blood pressure, including:
+ Severe headache or dizziness
+ Passing out or changes in eyesight
Signs of kidney problems, such as:
+ Inability to pass urine
+ Changes in urine output
+ Blood in the urine
+ Sudden weight gain
Signs of electrolyte problems, including:
+ Mood changes
+ Confusion
+ Muscle pain, cramps, or spasms
+ Weakness
+ Shakiness
+ Changes in balance
+ Abnormal heartbeat
+ Seizures
+ Loss of appetite
+ Severe nausea or vomiting
Unexplained bruising or bleeding
Feeling extremely tired or weak
Abnormal sensations, such as burning, numbness, or tingling
Chest pain or pressure, or a rapid heartbeat
Gum changes
Hearing loss
Shortness of breath
Shakiness
Swelling
Mouth irritation or mouth sores
Liver Problems
This medication can cause liver problems, which may be fatal. If you experience any of the following symptoms, contact your doctor immediately:
Dark urine
Fatigue
Decreased appetite
Nausea or stomach pain
Light-colored stools
Vomiting
Yellow skin or eyes
Progressive Multifocal Leukoencephalopathy (PML)
This medication can cause a rare and potentially fatal brain problem called PML. If you notice any of the following symptoms, contact your doctor right away:
Confusion
Memory problems
Depression
Changes in behavior
Weakness on one side of the body
Trouble speaking or thinking
Changes in balance or eyesight
Posterior Reversible Encephalopathy Syndrome (PRES)
This medication can also cause a rare and potentially fatal brain problem called PRES. If you experience any of the following symptoms, contact your doctor immediately:
Confusion
Decreased alertness
Changes in eyesight
Loss of eyesight
Seizures
Severe headache
Other Side Effects
Like all medications, this drug can cause side effects. Many people may not experience any side effects or may only have mild symptoms. If you notice any of the following side effects, contact your doctor if they bother you or do not go away:
Headache
Dizziness or drowsiness
Stomach pain or diarrhea
Nausea or vomiting
Gas
Hair growth
Acne
Flushing
Common cold symptoms
Joint pain
* Leg cramps
This is not a comprehensive list of all possible side effects. If you have questions or concerns about side effects, contact your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you notice any of the following symptoms, contact your doctor or seek immediate medical attention:
Signs of an allergic reaction, such as:
+ Rash
+ Hives
+ Itching
+ Red, swollen, blistered, or peeling skin with or without fever
+ Wheezing
+ Tightness in the chest or throat
+ Trouble breathing, swallowing, or talking
+ Unusual hoarseness
+ Swelling of the mouth, face, lips, tongue, or throat
Signs of high blood pressure, including:
+ Severe headache or dizziness
+ Passing out or changes in eyesight
Signs of kidney problems, such as:
+ Inability to pass urine
+ Changes in urine output
+ Blood in the urine
+ Sudden weight gain
Signs of electrolyte problems, including:
+ Mood changes
+ Confusion
+ Muscle pain, cramps, or spasms
+ Weakness
+ Shakiness
+ Changes in balance
+ Abnormal heartbeat
+ Seizures
+ Loss of appetite
+ Severe nausea or vomiting
Unexplained bruising or bleeding
Feeling extremely tired or weak
Abnormal sensations, such as burning, numbness, or tingling
Chest pain or pressure, or a rapid heartbeat
Gum changes
Hearing loss
Shortness of breath
Shakiness
Swelling
Mouth irritation or mouth sores
Liver Problems
This medication can cause liver problems, which may be fatal. If you experience any of the following symptoms, contact your doctor immediately:
Dark urine
Fatigue
Decreased appetite
Nausea or stomach pain
Light-colored stools
Vomiting
Yellow skin or eyes
Progressive Multifocal Leukoencephalopathy (PML)
This medication can cause a rare and potentially fatal brain problem called PML. If you notice any of the following symptoms, contact your doctor right away:
Confusion
Memory problems
Depression
Changes in behavior
Weakness on one side of the body
Trouble speaking or thinking
Changes in balance or eyesight
Posterior Reversible Encephalopathy Syndrome (PRES)
This medication can also cause a rare and potentially fatal brain problem called PRES. If you experience any of the following symptoms, contact your doctor immediately:
Confusion
Decreased alertness
Changes in eyesight
Loss of eyesight
Seizures
Severe headache
Other Side Effects
Like all medications, this drug can cause side effects. Many people may not experience any side effects or may only have mild symptoms. If you notice any of the following side effects, contact your doctor if they bother you or do not go away:
Headache
Dizziness or drowsiness
Stomach pain or diarrhea
Nausea or vomiting
Gas
Hair growth
Acne
Flushing
Common cold symptoms
Joint pain
* Leg cramps
This is not a comprehensive list of all possible side effects. If you have questions or concerns about side effects, contact your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
Seek Immediate Medical Attention If You Experience:
- Signs of infection: fever, chills, sore throat, cough, unusual fatigue, new pain, burning with urination.
- Signs of kidney problems: swelling in ankles/feet, decreased urine output, unusual weight gain, dark urine.
- Signs of liver problems: yellowing of skin or eyes (jaundice), dark urine, persistent nausea/vomiting, severe stomach pain.
- Signs of high blood pressure: severe headache, dizziness, blurred vision, pounding in ears.
- Neurological symptoms: tremor, seizures, confusion, numbness or tingling in hands/feet.
- Gum swelling or bleeding (gingival hyperplasia).
- Unusual hair growth (hirsutism).
- New lumps or growths on your body, or changes in existing moles.
- Unexplained muscle pain or weakness.
Before Using This Medicine
Before Taking This Medication: Important Information to Share with Your Doctor
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Be sure to describe the symptoms you experienced.
Certain health conditions, including:
+ Cancer
+ Kidney problems
+ High blood pressure
Other medications you are currently taking, such as:
+ Aliskiren
+ Amiloride
+ Bosentan
+ Dabigatran
+ Orlistat
+ Spironolactone
+ Triamterene
If you have psoriasis and are undergoing other treatments, including medications or radiation therapy.
Please note that this is not an exhaustive list of all potential interactions. This medication can interact with numerous other drugs, which may increase the risk of severe, life-threatening, or fatal side effects. Therefore, it is crucial to:
Inform your doctor and pharmacist about all your medications, including prescription and over-the-counter drugs, natural products, and vitamins.
Discuss your health problems with your doctor.
Verify that it is safe to take this medication with all your other medications and health conditions.
Do not start, stop, or modify the dose of any medication without consulting your doctor.
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Be sure to describe the symptoms you experienced.
Certain health conditions, including:
+ Cancer
+ Kidney problems
+ High blood pressure
Other medications you are currently taking, such as:
+ Aliskiren
+ Amiloride
+ Bosentan
+ Dabigatran
+ Orlistat
+ Spironolactone
+ Triamterene
If you have psoriasis and are undergoing other treatments, including medications or radiation therapy.
Please note that this is not an exhaustive list of all potential interactions. This medication can interact with numerous other drugs, which may increase the risk of severe, life-threatening, or fatal side effects. Therefore, it is crucial to:
Inform your doctor and pharmacist about all your medications, including prescription and over-the-counter drugs, natural products, and vitamins.
Discuss your health problems with your doctor.
Verify that it is safe to take this medication with all your other medications and health conditions.
Do not start, stop, or modify the dose of any medication without consulting your doctor.
Precautions & Cautions
It is essential to inform all your healthcare providers, including doctors, nurses, pharmacists, and dentists, that you are taking this medication. Before engaging in activities that require alertness, such as driving, wait until you understand how this drug affects you.
If you have diabetes (high blood sugar), it is crucial to monitor your blood sugar levels closely while taking this medication. Additionally, if you are using a salt substitute containing potassium, a potassium-sparing diuretic, or a potassium product, consult your doctor to discuss potential interactions.
This medication contains alcohol, so it is important to discuss this with your doctor. There is also an increased risk of skin cancer associated with this drug. To minimize this risk, limit your exposure to sunlight, sunlamps, and tanning beds, and use protective measures such as sunscreen, clothing, and eyewear. Regular skin checks, as recommended by your doctor, are also necessary.
Some individuals treated with this medication have developed severe kidney problems due to a viral infection (BK virus). This risk is particularly significant for those who have undergone a kidney transplant, as BK virus infection can lead to kidney loss. If you have concerns, consult your doctor.
Before receiving any vaccinations, discuss the potential risks and benefits with your doctor, as certain vaccines may not be effective or may increase the risk of infection when taken with this medication. Maintaining good oral hygiene through regular dental check-ups is also important.
Avoid consuming grapefruit and grapefruit juice while taking this medication. Additionally, be aware of the potential for gout attacks and monitor your condition accordingly.
If you are 65 years or older, use this medication with caution, as you may be more susceptible to side effects. Similarly, if the patient is a child, this medication should be used with caution, as the risk of certain side effects may be higher in children.
This medication may harm an unborn baby if taken during pregnancy. If you become pregnant or are planning to become pregnant, inform your doctor immediately. If you are breastfeeding, consult your doctor to discuss any potential risks to your baby.
If you have diabetes (high blood sugar), it is crucial to monitor your blood sugar levels closely while taking this medication. Additionally, if you are using a salt substitute containing potassium, a potassium-sparing diuretic, or a potassium product, consult your doctor to discuss potential interactions.
This medication contains alcohol, so it is important to discuss this with your doctor. There is also an increased risk of skin cancer associated with this drug. To minimize this risk, limit your exposure to sunlight, sunlamps, and tanning beds, and use protective measures such as sunscreen, clothing, and eyewear. Regular skin checks, as recommended by your doctor, are also necessary.
Some individuals treated with this medication have developed severe kidney problems due to a viral infection (BK virus). This risk is particularly significant for those who have undergone a kidney transplant, as BK virus infection can lead to kidney loss. If you have concerns, consult your doctor.
Before receiving any vaccinations, discuss the potential risks and benefits with your doctor, as certain vaccines may not be effective or may increase the risk of infection when taken with this medication. Maintaining good oral hygiene through regular dental check-ups is also important.
Avoid consuming grapefruit and grapefruit juice while taking this medication. Additionally, be aware of the potential for gout attacks and monitor your condition accordingly.
If you are 65 years or older, use this medication with caution, as you may be more susceptible to side effects. Similarly, if the patient is a child, this medication should be used with caution, as the risk of certain side effects may be higher in children.
This medication may harm an unborn baby if taken during pregnancy. If you become pregnant or are planning to become pregnant, inform your doctor immediately. If you are breastfeeding, consult your doctor to discuss any potential risks to your baby.
Overdose Information
Overdose Symptoms:
- Severe kidney dysfunction (marked increase in creatinine)
- Severe liver dysfunction
- Severe hypertension
- Neurological symptoms (tremor, seizures, confusion)
- Nausea, vomiting, abdominal pain
What to Do:
Seek immediate medical attention. Call 911 or your local emergency number. For poison control, call 1-800-222-1222. Treatment is primarily supportive; cyclosporine is not effectively removed by dialysis.
Drug Interactions
Contraindicated Interactions
- Bosentan (significant increase in cyclosporine levels)
- Aliskiren (increased aliskiren levels, potential for nephrotoxicity)
- Dabigatran (increased dabigatran levels)
- Statins (high doses, increased risk of myopathy/rhabdomyolysis)
- Live attenuated vaccines (due to immunosuppression)
Major Interactions
- CYP3A4 inhibitors (e.g., ketoconazole, fluconazole, voriconazole, erythromycin, clarithromycin, diltiazem, verapamil, grapefruit juice) - significantly increase cyclosporine levels, increasing toxicity risk.
- CYP3A4 inducers (e.g., rifampin, carbamazepine, phenytoin, phenobarbital, St. John's Wort, nafcillin) - significantly decrease cyclosporine levels, increasing rejection risk.
- Nephrotoxic agents (e.g., aminoglycosides, amphotericin B, NSAIDs, tacrolimus, sirolimus, ACE inhibitors, ARBs) - increased risk of nephrotoxicity.
- Potassium-sparing diuretics (e.g., spironolactone, amiloride, triamterene) - increased risk of hyperkalemia.
- Digoxin (increased digoxin levels)
- Colchicine (increased colchicine levels, increased risk of myopathy/neuropathy)
- Mycophenolate mofetil (decreased mycophenolate levels)
- Everolimus/Sirolimus (increased levels of both drugs, increased toxicity)
- Vaccines (reduced efficacy of vaccines, especially live vaccines)
Moderate Interactions
- Oral contraceptives (may increase cyclosporine levels)
- Metoclopramide (may increase cyclosporine levels)
- Cimetidine (may increase cyclosporine levels)
- Ranitidine (may increase cyclosporine levels)
- Allopurinol (may increase cyclosporine levels)
- Danazol (may increase cyclosporine levels)
- Methotrexate (increased risk of hepatotoxicity)
- Nifedipine (increased risk of gingival hyperplasia)
- Calcium channel blockers (some may increase cyclosporine levels)
- Warfarin (potential for altered INR, monitor closely)
Minor Interactions
- Not available (most interactions are clinically significant due to narrow therapeutic index)
Monitoring
Baseline Monitoring
Complete Blood Count (CBC)
Rationale: To establish baseline and monitor for potential hematologic abnormalities (e.g., anemia, leukopenia, thrombocytopenia).
Timing: Prior to initiation
Renal Function (Serum Creatinine, BUN, eGFR)
Rationale: To establish baseline renal function and monitor for nephrotoxicity, a common and serious adverse effect.
Timing: Prior to initiation
Liver Function Tests (ALT, AST, ALP, Bilirubin)
Rationale: To establish baseline hepatic function and monitor for hepatotoxicity.
Timing: Prior to initiation
Blood Pressure
Rationale: To establish baseline and monitor for hypertension, a common adverse effect.
Timing: Prior to initiation
Electrolytes (Potassium, Magnesium)
Rationale: To establish baseline and monitor for hyperkalemia and hypomagnesemia.
Timing: Prior to initiation
Lipid Profile (Total Cholesterol, LDL, HDL, Triglycerides)
Rationale: To establish baseline and monitor for dyslipidemia.
Timing: Prior to initiation
Uric Acid
Rationale: To establish baseline and monitor for hyperuricemia.
Timing: Prior to initiation
Routine Monitoring
Cyclosporine Trough Levels (C0 or C2)
Frequency: Initially 2-3 times per week until stable, then at least weekly for the first month, then every 2-4 weeks or as clinically indicated.
Target: Highly variable based on indication, time post-transplant, and assay method (e.g., 100-400 ng/mL for C0 in early post-transplant, lower for maintenance; 800-1200 ng/mL for C2 in early post-transplant). Refer to institutional protocols and clinical guidelines.
Action Threshold: Levels outside target range require dose adjustment and re-monitoring. Supratherapeutic levels increase toxicity risk; subtherapeutic levels increase rejection risk.
Renal Function (Serum Creatinine, BUN)
Frequency: At least twice weekly for the first month, then weekly for 2-3 months, then monthly or as clinically indicated.
Target: Maintain within acceptable limits, ideally <30% increase from baseline.
Action Threshold: Persistent increase in SCr >30% from baseline (or >25% in RA/psoriasis) may indicate nephrotoxicity and requires dose reduction or discontinuation.
Liver Function Tests (ALT, AST, ALP, Bilirubin)
Frequency: Weekly for the first month, then monthly or as clinically indicated.
Target: Within normal limits.
Action Threshold: Significant elevation may indicate hepatotoxicity and requires dose adjustment or discontinuation.
Blood Pressure
Frequency: Daily initially, then weekly, then monthly or as clinically indicated.
Target: <130/80 mmHg (or as per clinical guidelines for transplant patients).
Action Threshold: Persistent hypertension requires antihypertensive therapy.
Electrolytes (Potassium, Magnesium)
Frequency: Weekly for the first month, then monthly or as clinically indicated.
Target: Potassium: 3.5-5.0 mEq/L; Magnesium: 1.5-2.5 mg/dL.
Action Threshold: Hyperkalemia or hypomagnesemia requires intervention (e.g., dietary changes, supplements, medication adjustment).
Complete Blood Count (CBC)
Frequency: Monthly or as clinically indicated.
Target: Within normal limits.
Action Threshold: Significant abnormalities (e.g., anemia, leukopenia) require investigation.
Lipid Profile
Frequency: Every 3-6 months or as clinically indicated.
Target: Within target ranges for cardiovascular risk.
Action Threshold: Dyslipidemia may require lipid-lowering therapy.
Symptom Monitoring
- Signs of infection (fever, chills, sore throat, unusual fatigue, new pain)
- Signs of kidney problems (decreased urine output, swelling in ankles/feet, unusual weight gain)
- Signs of liver problems (yellowing of skin/eyes, dark urine, persistent nausea/vomiting, abdominal pain)
- Signs of high blood pressure (headache, dizziness, blurred vision)
- Signs of neurological issues (tremor, seizures, confusion, paresthesias)
- Signs of gingival hyperplasia (gum swelling, bleeding)
- Signs of hirsutism (unusual hair growth)
- Signs of malignancy (new lumps, persistent sores, unexplained weight loss)
- Muscle pain or weakness (especially if taking statins)
Special Patient Groups
Pregnancy
Cyclosporine is Pregnancy Category C. It should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Data from transplant registries suggest no increased risk of major birth defects, but there is an increased risk of prematurity and low birth weight. Close monitoring of the mother and fetus is essential.
Trimester-Specific Risks:
First Trimester:
Potential for increased risk of prematurity and low birth weight, but no consistent pattern of major congenital malformations observed in human data.
Second Trimester:
Continued risk of prematurity and low birth weight. Close monitoring of maternal cyclosporine levels and renal function.
Third Trimester:
Continued risk of prematurity and low birth weight. Neonatal immunosuppression is possible, though rare. Monitor neonate for signs of infection.
Lactation
Cyclosporine is excreted into breast milk. Due to the potential for serious adverse reactions in the breastfed infant (e.g., immunosuppression, nephrotoxicity, increased risk of malignancy), breastfeeding is not recommended during cyclosporine therapy.
Infant Risk:
High (L4 - Possibly hazardous)
Pediatric Use
Dosing is highly individualized based on weight, body surface area, and therapeutic drug monitoring (TDM). Children may require higher doses per kg than adults due to faster metabolism. Long-term effects on growth and development should be monitored. Increased susceptibility to infection and malignancy is a concern.
Geriatric Use
No specific dose adjustments are generally required based solely on age, but elderly patients may have age-related decreases in renal or hepatic function, which necessitate dose adjustments and closer monitoring. They may also be more susceptible to adverse effects like hypertension and nephrotoxicity.
Clinical Information
Clinical Pearls
- Neoral (modified cyclosporine) has improved and more consistent bioavailability compared to the original Sandimmune formulation. They are NOT interchangeable on a milligram-for-milligram basis; conversion requires careful monitoring and dose adjustment.
- Therapeutic drug monitoring (TDM) of cyclosporine trough levels (C0) or 2-hour post-dose levels (C2) is crucial for optimizing efficacy and minimizing toxicity, especially in transplant patients.
- Nephrotoxicity is a dose-limiting and common side effect. Regular monitoring of renal function (SCr, BUN) is paramount. An increase in SCr >30% from baseline often warrants dose reduction.
- Hypertension is common and often requires antihypertensive therapy. Calcium channel blockers (e.g., amlodipine) are often preferred as they do not significantly interact with cyclosporine metabolism (unlike diltiazem/verapamil).
- Many drug interactions exist, particularly with CYP3A4 inhibitors/inducers and nephrotoxic agents. Always review concomitant medications carefully.
- Patients are at increased risk of infections (bacterial, viral, fungal, opportunistic) and malignancies (especially skin cancer and post-transplant lymphoproliferative disorder, PTLD). Educate patients on sun protection and symptom recognition.
- Gingival hyperplasia and hirsutism are common cosmetic side effects that can impact patient adherence.
Alternative Therapies
- Tacrolimus (another calcineurin inhibitor, often preferred due to lower rates of hypertension, dyslipidemia, and hirsutism, but higher rates of new-onset diabetes and neurotoxicity)
- Sirolimus (mTOR inhibitor)
- Everolimus (mTOR inhibitor)
- Mycophenolate Mofetil (antiproliferative agent)
- Azathioprine (antiproliferative agent)
- Corticosteroids (e.g., Prednisone)
- Belatacept (co-stimulation blocker)
- Rituximab (CD20 monoclonal antibody, for certain autoimmune conditions)
- Methotrexate (for RA/psoriasis)
- Biologic DMARDs (for RA/psoriasis, e.g., TNF inhibitors, IL-17 inhibitors)
Cost & Coverage
Average Cost:
$200 - $800+ per 30 capsules (25mg)
Generic Available:
Yes
Insurance Coverage:
Tier 3 (Preferred Brand) or Tier 4 (Non-Preferred Brand) for brand; Tier 1/2 for generic. Often requires prior authorization.
General Drug Facts
If your symptoms or health issues persist or worsen, it's essential to contact your doctor for further guidance. To ensure your safety, never share your medication with others or take someone else's medication. Some medications may come with an additional patient information leaflet, so be sure to check with your pharmacist for more details. If you have any questions or concerns about your medication, don't hesitate to reach out to your doctor, nurse, pharmacist, or other healthcare provider. In the event of a suspected overdose, immediately call your local poison control center or seek emergency medical attention. When seeking help, be prepared to provide information about the medication taken, the amount, and the time it occurred.