Cyclosporine Capsules: Dosage, Indications, Contraindications, and Side Effects

Overview:

Cyclosporine is a pivotal immunosuppressive agent, vital in medical applications such as organ transplantation and autoimmune diseases like rheumatoid arthritis. Derived from the fungus Beauveria nivea, it is an 11-amino acid cyclic polypeptide prominently featured in pharmaceutical formulations. This potent drug modulates the immune response, preventing rejection in transplants and alleviating inflammatory processes in autoimmune conditions. Cyclosporine was approved by the United States Food and Drug Administration (USFDA) in January 2000. The article delves into understanding its mechanisms and applications and underscores its significance in modern medicine.

Drug Group:

Cyclosporine belongs to the drug class known as immunosuppressants. These drugs suppress the immune system and are frequently employed to inhibit the rejection of newly transplanted organs and for certain autoimmune diseases.

Indications:

Cyclosporine capsules are used for various medical conditions to suppress the immune system.

Here are some common indications for the use of Cyclosporine capsules:

• Organ Transplantation: Prevention of rejection in organ transplant recipients (for example, kidney, liver, heart).

• Autoimmune Diseases: Treatment of autoimmune disorders such as rheumatoid arthritis (affects joints, causing inflammation and potential deformities) and psoriasis (leads to skin plaques and can involve joints).

• Atopic Dermatitis (Eczema): Management of severe cases of atopic dermatitis (eczema) when other treatments are ineffective.

• Graft-versus-Host Disease (GVHD): The prevention and treatment of graft-versus-host disease can occur after bone marrow or stem cell transplantation.

• Nephrotic Syndrome: Treatment of nephrotic syndrome, a kidney disorder characterized by proteinuria (proteins in the blood) and edema (swelling).

• Inflammatory Bowel Disease: In some cases, Cyclosporine may be used for severe or refractory inflammatory bowel diseases like Crohn's disease (which impacts any part of the gastrointestinal [GI] tract) and ulcerative colitis (which affects the colon and rectum).

Available Doses and Dosage Forms:

Dosage Form: Soft gelatin capsules (Cyclosporine capsules, USP)

Available Strengths: 25 mg (milligrams) and 100 mg.

Composition per 25 mg Capsule:

• Cyclosporine, USP (United States pharmacopeia): 25 mg.

• Dehydrated alcohol, USP: Max 12.7 percent by volume.

• Inactive Ingredients: Corn oil, gelatin, iron oxide red, linoleoyl macrogolglycerides, sorbitol, and titanium dioxide.

Composition per 100 mg Capsule:

• Cyclosporine, USP: 100 mg.

• Dehydrated alcohol, USP: Max 12.7 percent by volume.

• Inactive Ingredients: Corn oil, gelatin, iron oxide red, linoleoyl macrogolglycerides, sorbitol, and titanium dioxide.

• It may contain glycerol; 100 mg capsules may contain iron oxide yellow.

For Patients:

What Is Rheumatoid Arthritis and Transplant Rejection?

• Rheumatoid Arthritis (RA): Rheumatoid arthritis is a persistent autoimmune condition predominantly impacting the joints. In this disorder, the immune system targets the synovium, the membrane lining around the joints. This results in inflammation, pain, rigidity, and ultimately, damage and deformities in the joints. RA typically impacts bilateral joints, including the hands, wrists, and knees. It may also impact various organs and systems in the body. Treatment typically involves medications, including disease-modifying antirheumatic drugs (DMARDs) like Cyclosporine, to suppress the immune response and reduce inflammation.

• Transplant Rejection: Transplant rejection refers to the immune system's response to a transplanted organ or tissue as if it were a foreign invader. The immune system's job is to recognize and eliminate anything foreign or harmful to the body. When a person undergoes organ transplantation, the recipient's immune system might recognize the transplanted organ as foreign and initiate an immune reaction to reject it. Immunosuppressive medications, such as Cyclosporine, are crucial in preventing transplant rejection. These drugs suppress the immune system, reducing its ability to attack and reject the transplanted organ. Close monitoring and careful management of immunosuppressive medications are essential to maintain the balance between preventing rejection and avoiding complications associated with excessive immunosuppression, such as infections.

How Do Cyclosporine Capsules Work?

Cyclosporine capsules work by suppressing the immune system. As an immunosuppressive agent, Cyclosporine interferes with the activity of certain immune cells, particularly T-cells. T-cells are involved in the immune system's response, and by inhibiting their function, Cyclosporine helps to modulate and reduce the overall immune response.

In rheumatoid arthritis, Cyclosporine helps control the inflammatory process by dampening the immune system's attack on the joints.

For transplant recipients, the goal is to prevent organ rejection. When a person undergoes organ transplantation, the body's immune system might identify the transplanted organ as foreign and attempt to reject it. Cyclosporine helps prevent this rejection by suppressing the immune response against the transplanted organ.

What Is the Dosage of Cyclosporine Capsules?

The dosage is as follows:

Organ Transplantation:

• To prevent rejection in individuals who have undergone transplantation, the initial dosage is often higher and is gradually reduced over time.

• Typical starting doses might be around eight to 12 mg/kg (milligrams per kilogram of body weight) per day, divided into two doses.

Autoimmune Conditions (Rheumatoid Arthritis and Psoriasis):

• Lower maintenance doses are often used for the treatment of autoimmune conditions.

• Dosages may start at around 2.5 to 5 mg/kg daily, divided into two doses.

How Effective Is Cyclosporine Capsules?

Cyclosporine is an immunosuppressive medication used for conditions like severe psoriasis or, less commonly, rheumatoid arthritis. Its effectiveness varies, and it is often used in the short term due to potential side effects like kidney toxicity. In clinical studies, Cyclosporine has demonstrated effectiveness in certain cases, particularly in treating severe psoriasis. However, it is important to note that its use is often limited to short-term courses due to potential side effects, and it may not be suitable for everyone.

What Are the Things to Inform the Doctor Before Taking Cyclosporine Capsules?

Before starting Cyclosporine capsules, informing the doctor about various aspects of health is crucial to ensuring safe and effective use. Here are key things to discuss with the healthcare provider:

• Medical History: Inform the doctor about any pre-existing medical conditions one may have, especially kidney disease, high blood pressure, liver disease, infections, or a history of cancer. Discuss any history of allergic reactions to medications.

• Current Medications: Give a complete list of all the medicines the patient is taking, whether they are prescribed or bought without a prescription, including vitamins and supplements that the patient is currently taking, as well as any herbal supplements or alternative therapies.

• Pregnancy and Breastfeeding: Inform about pregnancy, planning to become pregnant, or breastfeeding. Cyclosporine may have potential risks during pregnancy.

• Vaccinations: Update the doctor on any recent vaccinations or plans for vaccination, as Cyclosporine may affect one’s response to certain vaccines.

• Infections: Report any current or recent infections to the doctor. Cyclosporine can suppress the immune system, and infections may need to be treated before starting the medication.

• Allergies: Inform the doctor about any allergies, especially if the patient has had allergic reactions to Cyclosporine or other medications.

• Previous Medication Use: If one has previously used immunosuppressive medications, share that information with the doctor.

• Skin Conditions: For individuals using Cyclosporine for psoriasis, provide details about the skin condition, including the severity and duration of symptoms.

• Routine Health Checkup: Ensure one has had recent blood tests, including kidney function tests and blood pressure measurements. Cyclosporine can affect the kidneys, and regular monitoring is essential.

• Smoking and Alcohol Use: Inform the doctor about smoking and alcohol habits, as these factors may influence the choice of treatment.

How Are Cyclosporine Capsules Administered?

Cyclosporine capsules should be administered twice daily on a consistent schedule, irrespective of meals. Avoiding grapefruit or grapefruit juice is recommended, as it can affect the metabolism of Cyclosporine, leading to increased blood concentrations.

What Are the Side Effects of Cyclosporine Capsules?

The side effects are as follows:

Kidney, Liver, and Heart Transplantation:

• Adverse reactions to Cyclosporine therapy include renal dysfunction (impaired kidney function), tremors (involuntary shaking or trembling of hands, limbs, or other body parts), hirsutism (abnormal and excessive hair growth), hypertension (high blood pressure), and gum hyperplasia (overgrowth of gum tissue).

• Hypertension occurs in about 50 percent of renal transplant patients and most cardiac transplant patients.

• Glomerular capillary thrombosis (blood clot formation in the tiny vessels of the kidney) and hypomagnesemia (low magnesium levels).

• Infections and postmarketing experiences highlight hepatotoxicity (liver toxicity), increased infection risk, and neurological complications.

Rheumatoid Arthritis:

• Adverse reactions involve renal (kidney) dysfunction, hypertension, headaches, and gastrointestinal disturbances. Controlled trials provide insights into adverse events in rheumatoid arthritis patients.

Dietary Considerations:

It is necessary to avoid grapefruit and grapefruit juice, as they can increase Cyclosporin blood concentrations. Maintain a consistent schedule for taking the capsules concerning meals. Ensure a balanced diet as well.

Missed Dose:

If a dose of Cyclosporine capsules is missed, it should be taken as soon as remembered. However, if it is almost time for the next scheduled dose, skip the missed dose and adhere to the regular dosing schedule. Taking an extra dose to make up for a missed one should be avoided. Suppose there are questions or concerns about missed doses. In that case, it is advisable to consult with a doctor, provider, or pharmacist for guidance based on the specific medical condition and treatment plan.

Overdose:

Cyclosporin overdose can lead to severe symptoms, including nausea, vomiting, seizures, and kidney dysfunction. Immediate medical attention is crucial. Gastric lavage and activated charcoal may be employed to remove unabsorbed Cyclosporin. Symptomatic treatment addresses specific manifestations while adjusting or discontinuing Cyclosporin, helps reduce blood concentrations.

Monitoring vital signs and organ function closely is important, and supportive care is provided as needed. In severe cases, hemodialysis (a medical procedure for filtering blood to remove waste and excess fluids when the kidneys cannot perform this function effectively) may be considered to enhance Cyclosporin removal. Seeking professional medical assistance is imperative for the appropriate evaluation and management of Cyclosporin overdose.

Storage

It is necessary to keep and distribute from the original single-dose container at a controlled room temperature of 68 degrees Fahrenheit to 77 degrees Fahrenheit (20 degrees Celsius to 25 degrees Celsius).

For Doctors:

Chemical Composition:

Cyclosporine is denoted as cyclic-(L-alanyl-D-alanyl-N-methyl-L-leucyl-N-methyl-L-leucyl-N-methyl-L-valyl-3-hydroxy-N,4-dimethyl-L-2-amino-6-octenoyl-L-α-aminobutyryl-N-methylglycyl-N-methyl-L-leucyl-L-valyl-N-methyl-L-leucyl).

Dose:

Dosing Guidelines for Organ Transplantation in Adults:

Oral Administration:

• Four to 12 Hours Before the Transplant: Take a single oral dose of 14 to 18 mg/kg.

• One to Two Weeks After the Transplant: Take 5 to 15 mg/kg per day orally, divided into two doses.

• Gradual Reduction: Decrease the dose by five percent each week until reaching 5 to 10 mg/kg per day orally, divided into two doses.

Focal Segmental Glomerulosclerosis: The recommended oral dosage is 3 mg/kg daily, administered every 12 hours.

Rheumatoid Arthritis: For the oral (modified) form, start with a dose of 2.5 mg/kg daily, taken every 12 hours. If there is an inadequate response after eight weeks, consider increasing the dosage by 0.5 to 0.75 mg/kg daily. The daily dosage should not exceed 4 mg/kg.

Psoriasis: In the case of the oral (modified) formulation, start with an initial dosage of 2.5 mg/kg per day, administered every 12 hours. If the desired response is not achieved after four weeks, an incremental increase of 0.5 mg/kg per day may be considered. The maximum recommended daily dose is 4 mg/kg.

Dosing Considerations:

• Renal Impairment: Cyclosporine's pharmacokinetics are minimally affected by routine hemodialysis in end-stage renal disease. Due to its nephrotoxic potential, renal function should be closely monitored, and dosage should be adjusted if needed. Patients with impaired renal function, rheumatoid arthritis, or psoriasis should avoid Cyclosporine.

• Hepatic Impairment: Severe liver disease may reduce Cyclosporine clearance, requiring dose adjustments to maintain recommended blood concentrations.

• Newly Transplanted Patients: Cyclosporine's initial dose depends on the transplanted organ. Dosage adjustments are based on blood concentrations. Adrenal Corticosteroids are recommended initially, with gradual tapering.

• Transplant Patients with Poor Absorption: Individualized dosing is crucial, with frequent monitoring to stabilize blood trough concentrations.

• Rheumatoid Arthritis: Cyclosporine's initial dose is 2.5 mg/kg/day, adjusted based on clinical response. Tapering of Prednisone is recommended, and dose adjustments may be necessary for adverse events.

What Are the Pharmacological Aspects of Cyclosporine Capsules?

Pharmacodynamics

• Cyclosporine serves as a potent immunosuppressive agent, effectively prolonging the survival of allogeneic transplants in animals, encompassing various organs such as skin, kidney, liver, heart, pancreas, bone marrow, small intestine, and lungs.

• Demonstrated effects of Cyclosporine include suppressing the inhibition of humoral immunity and, to a greater degree, cellular immune responses. These reactions encompass allograft rejection, delayed hypersensitivity, experimental allergic encephalomyelitis, Freud’s adjuvant arthritis, and graft versus host disease across numerous animal species and organ types.

• Cyclosporine's effectiveness arises from its targeted and reversible blocking of immunocompetent lymphocytes during the G0 and G1 phases of the cell cycle, with a preferential focus on T-lymphocytes. The primary target is the T-helper cell, although the T-suppressor cell may also be affected. Additionally, Cyclosporine inhibits the production and release of lymphokines, including interleukin-2.

• Importantly, no discernible effects on phagocytic function, such as changes in enzyme secretions, chemotactic migration of granulocytes, macrophage migration, or carbon clearance in vivo, have been observed in animals. Furthermore, Cyclosporine does not induce bone marrow suppression in animal models or humans.

Mechanism

Cyclosporin, a potent immunosuppressive drug, primarily exerts its effects by inhibiting the activity of calcineurin, a crucial enzyme in T-cell activation. The mechanism involves the following steps:

Calcineurin Inhibition:

• Cyclosporin binds to cyclophilin, forming a complex.

• This complex inhibits calcineurin, preventing its activation.

T-Cell Activation Blockade:

• Inhibition of Calcineurin hinders the activation of T-cells.

• T-cells have a central role in the immune response.

Cytokine Production Reduction:

• T-cell activation usually leads to cytokine production, essential for immune responses.

• Cyclosporin's action results in reduced cytokine production, such as interleukin-2.

Suppression of Immune Response:

• With decreased cytokine production, there is suppression of the immune response.

• This is particularly valuable in preventing rejection of transplanted organs and treating autoimmune diseases.

Pharmacokinetics

• Absorption: The immunosuppressive effect of Cyclosporine is primarily attributed to the parent drug. Upon oral administration, the absorption of Cyclosporine is incomplete. The degree of absorption is subject to variability among individual patients, the patient population, and the specific formulation.

• Elimination: Cyclosporine is predominantly eliminated through biliary pathways, with only six percent of the administered dose (comprising both the parent drug and metabolites) excreted in urine.

• Disposition: The elimination of Cyclosporine from the bloodstream typically follows a biphasic pattern, with a terminal half-life of approximately 8.4 hours (range: five to 18 hours). After intravenous administration, blood clearance of Cyclosporine ranges from approximately five to seven mL/min/kg (milliliters per minute per kilogram of body weight) in adult recipients of renal or liver allografts. Cardiac transplant patients may exhibit slightly slower blood clearance.

• Bioequivalence: The impact of milk on the bioavailability of Cyclosporine when administered as Cyclosporine has not been assessed.

• Dose-Exposure Relationship: The relationship between the administered dose and exposure is linear within the therapeutic dose range.

Toxicity:

In cases of toxicity, priority should be given to establishing a clear airway. Monitoring for signs of respiratory insufficiency is crucial, and ventilation assistance should be provided if necessary. Healthcare providers should also be vigilant for shock, administering treatment as needed. Anticipating and addressing seizures (sudden, uncontrolled electrical disturbances in the brain), along with initiating supportive and symptomatic care, is essential. In instances of Cyclosporine overdosage, healthcare providers may temporarily withhold the drug or initiate alternate-day therapy until the patient stabilizes.

Hemodialysis, a medical procedure that filters and cleanses the blood outside the body, is typically used for kidney failure; it eliminates only one percent of the dose. Monitoring serum CsA (Cyclosporine A levels) levels is mandatory, with the potential for multiple dose adjustments during treatment. The CVC (central venous catheter line) line is not used to infuse CsA. Still, it can safely collect blood samples for serum CsA levels, following proper techniques for discarding five mL of blood immediately after interrupting the infusion.

Clinical Studies:

The efficacy of Cyclosporin capsules in addressing severe rheumatoid arthritis was assessed through five clinical studies, encompassing 728 patients treated with Cyclosporine and 273 patients on a placebo. The responder rates per treatment group are summarized, where a responder is defined as a patient completing the trial with a 20 percent improvement in both tender and swollen joint counts and a 20 percent improvement in two of four specified criteria.

In Study 651, 264 patients with active rheumatoid arthritis were enrolled and randomized into three groups:

• Cyclosporine at 2.5 to 5 mg/kg/day.

• Methotrexate at 7.5 to 15 mg/week.

• Placebo.

The treatment duration was 24 weeks, and at the final visit, the average Cyclosporine dosage was 3.1 mg/kg/day.

Study 652 involved 250 patients with active rheumatoid arthritis, randomizing them into three treatment arms:

• 1.5 to 5 mg/kg/day of Cyclosporine.

• 2.5 to 5 mg/kg/day of Cyclosporine.

• Placebo.

The treatment duration was 16 weeks, and at the last visit, the average Cyclosporine dosage for Group 2 was 2.92 mg/kg/day.

In Study 2008, 144 patients with active rheumatoid arthritis were enrolled and randomized into two groups.

• Cyclosporine was administered at 2.5 to 5 mg/kg/day with adjustments to reach a target trough level.

• Placebo.

The treatment duration was 24 weeks, and at the final visit, the average Cyclosporine dosage was 3.63 mg/kg/day.

Study 654 included 148 patients with active joint counts of 6 or more despite maximally tolerated methotrexate doses. Patients were randomized to receive either.

• Cyclosporine 2.5 mg/kg/day with dose adjustments.

• Placebo, in addition to the current Methotrexate dose.

The treatment duration was 24 weeks, and the mean Cyclosporine dose at the last visit was 2.8 mg/kg/day.

What Are the Contraindications of Cyclosporine Capsules?

The contraindications are as follows:

• Cyclosporine capsules are not recommended for individuals with hypersensitivity to Cyclosporine or any of the components in the formulation.

• Patients with rheumatoid arthritis with abnormal kidney function, uncontrolled hypertension, or malignancies should refrain from using Cyclosporine capsules.

• Psoriasis patients undergoing Cyclosporine capsule treatment should refrain from concurrent use of PUVA or UVB therapy, Methotrexate, other immunosuppressive agents, coal tar, or radiation therapy. Additionally, individuals with psoriasis and abnormal renal function, uncontrolled hypertension, or malignancies are advised against receiving Cyclosporine capsules.

Warnings and Precautions: The following are the warnings associated with:

1. All Patients: Cyclosporine has the potential to induce nephrotoxicity and hepatotoxicity, with the risk escalating with higher Cyclosporine doses. Renal dysfunction, including structural damage to the kidneys, is a plausible consequence of Cyclosporine use, necessitating regular monitoring of renal function during therapy. Caution is advised when coadministering Cyclosporine with the nephrotoxic drugs.

Patients receiving Cyclosporine require frequent monitoring of serum creatinine levels, especially in the elderly, as age-related decrease in renal function may occur. Inadequate monitoring and improper dose adjustments may lead to structural kidney damage and persistent renal dysfunction.

During Cyclosporine therapy, an increase in serum creatinine and BUN (blood urea nitrogen) may occur, reflecting a decrease in the glomerular filtration rate. Structural kidney damage and persistent renal dysfunction may ensue without proper dose reduction or discontinuation.

2. Kidney, Liver, and Heart Transplant

• Nephrotoxicity: Cyclosporine can induce nephrotoxicity and hepatotoxicity at higher doses, leading to elevated serum creatinine and BUN levels. The increased levels in patients with renal transplants do not necessarily suggest rejection and a thorough patient evaluation is essential before initiating dosage adjustments. Based on historical Cyclosporine experience, nephrotoxicity associated with Cyclosporine was noted in 25 percent of renal transplant cases, 38 percent of cardiac transplant cases, and 37 percent of liver transplant cases. Mild nephrotoxicity typically occurs two to three months post-renal transplant, with manifestations such as a plateau in pre-operative BUN and creatinine elevations. Such mild nephrotoxicity responded well to Cyclosporine dosage reduction. More severe nephrotoxicity, characterized by a rapid increase in BUN and creatinine, occurred early after transplantation and often necessitated Cyclosporine dosage reduction. It is crucial to differentiate between nephrotoxicity and rejection, as they may present similar clinical features.

• Nephrotoxicity vs. Rejection: Several parameters may help distinguish nephrotoxicity from rejection, but up to 20 percent of patients may experience simultaneous nephrotoxicity and rejection. Careful monitoring and frequent dosage adjustments may be necessary in cases of impaired renal function. A form of Cyclosporine-associated nephropathy, characterized by a progressive deterioration in renal function and morphological changes, may occur in 5 to 15 percent of transplant recipients. This condition may persist despite decreasing or discontinuing Cyclosporine therapy and requires evidence from renal biopsies for diagnosis. The reversibility of interstitial fibrosis and its correlation with renal function remains undetermined. While arteriolopathy reversibility has been reported, caution is advised to avoid excessive immunosuppression, especially in severe and unremitting rejection episodes. Caution should be exercised when coadministering Cyclosporine with drugs that may impair renal function due to potential additive or synergistic effects.

3. Thrombotic Microangiopathy:

In rare instances, patients have developed thrombocytopenia and microangiopathic hemolytic anemia, leading to graft failure. Detection and management of this syndrome involve platelet studies and early intervention, including streptokinase, heparin, or plasmapheresis.

4. Hyperkalemia: Individual patients have occasionally experienced notable hyperkalemia, sometimes linked with hyperchloremic metabolic acidosis and hyperuricemia.

5. Hepatotoxicity: Hepatotoxicity, manifesting as elevated hepatic enzymes and bilirubin, has been reported in the trials, particularly in the first month of therapy with high Cyclosporine doses. Monitoring for hepatotoxicity is crucial, especially in patients with comorbidities and confounding factors. Fatal outcomes have been reported, primarily in transplant patients.

6. Malignancies: Individuals taking Cyclosporine are at an elevated risk of developing lymphomas and other malignancies, particularly skin cancers. Avoidance of excessive ultraviolet light exposure is recommended, and the risk is associated with the intensity and duration of immunosuppression. Caution is advised when using a treatment regimen containing multiple immunosuppressants due to the potential for over-suppression of the immune system, increasing the risk of infection or malignancy.

7. Serious Infections: Immunosuppressed patients, including those receiving Cyclosporine, are at an increased risk of infections caused by bacteria, viruses, fungi, and protozoa, including opportunistic infections. These infections may have serious, including fatal, outcomes.

8. Polyoma Virus Infections: Patients with suppressed immune systems face an elevated risk of opportunistic infections, including polyoma virus infections. Serious outcomes, such as JC virus-associated progressive multifocal leukoencephalopathy (PML) and polyoma virus-associated nephropathy (PVAN), have been observed in patients receiving Cyclosporine. PVAN can lead to deteriorating renal function and renal graft loss, requiring careful monitoring of patients at risk.

9. Neurotoxicity: Reports of convulsions in patients receiving Cyclosporine, particularly in combination with high-dose Methylprednisolone, have been documented. Encephalopathy, including posterior reversible encephalopathy syndrome (PRES), has been described in post-marketing reports. Manifestations include impaired consciousness, convulsions, visual disturbances, loss of motor function, movement disorders, and psychiatric problems. Factors predisposing to neurotoxicity include hypertension, hypomagnesemia, hypocholesterolemia, high-dose corticosteroids, high Cyclosporine blood concentrations, and graft-versus-host disease. Changes are often reversible upon discontinuation or dose reduction of Cyclosporine, particularly in liver transplant patients. Optic disc edema, including papilloedema, with potential visual impairment, has been reported, primarily in transplant patients.

10. Rheumatoid Arthritis: In rheumatoid arthritis patients, Cyclosporine nephropathy was detected in renal biopsies of 10 percent of patients after an average treatment duration of 19 months. A higher risk of malignant lymphomas is associated with Cyclosporine use. Evaluation for malignancies is recommended before and during Cyclosporine treatment.

11. Psoriasis: Administering Cyclosporine to psoriasis patients necessitates a thoughtful evaluation of the associated risks and benefits due to its potent immunosuppressive nature. The risks of nephrotoxicity and hypertension rise with increased doses and prolonged therapy, particularly in individuals with impaired renal function, uncontrolled hypertension, or malignancies. Renal function must be closely monitored, and caution is advised regarding sun exposure. Psoriasis patients treated with Cyclosporine capsules are at increased risk of skin and lymphoproliferative malignancies. The relative risk is similar to what is seen in psoriasis patients treated with alternative immunosuppressive agents.

12. Special Excipients: The alcohol content of Cyclosporine should be considered, especially in patients where alcohol intake should be minimized. For an adult weighing 154 pounds, the maximum daily oral dose delivers approximately six percent of the amount of alcohol in a standard drink. Special attention is needed for patients such as pregnant or breastfeeding women, those with liver disease or epilepsy, alcoholics, or pediatric patients.

The precautions associated with Cyclosporine treatment are

1. General Precautions:

• Hypertension: Cyclosporine commonly induces hypertension, with mild or moderate cases being more frequent than severe ones. Antihypertensive therapy may be necessary, but caution is needed with potassium-sparing diuretics due to the potential for hyperkalemia. Calcium antagonists can be effective but may interfere with Cyclosporine metabolism.

• Vaccination: During Cyclosporine treatment, vaccination may be less effective, and live attenuated vaccines should be avoided.

2. Prescribing Warning: Cyclosporine, a systemic immunosuppressant, must be prescribed by experienced physicians familiar with managing immunosuppressive therapy. Specialized care is essential for solid organ transplantation doses.

3. Facility Needs: Patients on Cyclosporine require management in well-equipped facilities with adequate medical resources. The responsible physician should possess detailed patient follow-up information.

4. Immunosuppression Risks: Cyclosporine elevates infection susceptibility and neoplasia development, especially in transplant patients receiving other immunosuppressive agents.

5. Bioavailability Variation: Cyclosporine is not interchangeable without physician oversight. Cyclosporine has a higher bioavailability, impacting Cyclosporine blood concentrations. Monitoring is crucial for transplant and rheumatoid arthritis patients to prevent toxicity or rejection.

6. Special Monitoring for Rheumatoid Arthritis Patients: Before starting treatment, blood pressure and creatinine levels should be assessed, and regular monitoring should be performed during the initial months. If hypertension occurs, consider dose reduction or antihypertensive agents.

7. Special Monitoring for Psoriasis Patients: Conduct a thorough dermatological and physical examination before treatment initiation. Monitor blood pressure, serum creatinine, and other lab values regularly. Low starting doses and careful monitoring help reduce the risk of Cyclosporine nephropathy.

8. Information for Patients: Advise patients on cautious formulation changes and the need for repeated laboratory tests during Cyclosporine therapy. Inform about potential risks during pregnancy, such as increased neoplasia risk, hypertension, and renal dysfunction.

9. Laboratory Tests: Regularly assess renal and liver functions, serum lipids, magnesium, potassium, and Cyclosporine blood concentrations in all patients treated with Cyclosporine. For transplant patients, routine blood concentration monitoring is essential.

What Are the Drug Interactions of Cyclosporine Capsules?

1. Drugs Potentiating Renal Dysfunction:

• NSAIDs.

• Antibiotics (Entamicin, Vancomycin).

• Antifungals (Ketoconazole, Fluconazole).

• Immunosuppressives (Tacrolimus, Mycophenolate).

2. Drugs Increasing Cyclosporine Concentrations:

• Calcium Channel Blockers (Diltiazem, Verapamil).

• Antifungals (Itraconazole, Voriconazole).

• Antibiotics (Clarithromycin, Erythromycin).

• Glucocorticoids (Methylprednisolone).

• Other drugs (Amiodarone, Colchicine).

3. Drugs Decreasing Cyclosporine Concentrations:

• Antibiotics (Rifampin, Nafcillin).

• Anticonvulsants (Carbamazepine, Phenytoin).

• Other drugs (Bosentan, St. John’s Wort).

4. Specific Drug Interactions:

• Bosentan.

• Boceprevir and Telaprevir.

• Grapefruit juice.

5. Drugs Affected by Cyclosporine:

• Digoxin.

• Colchicine.

• Statins (Lovastatin, Simvastatin).

• Repaglinide.

• Ambrisentan.

• Anthracycline antibiotics (Doxorubicin).

6. Other Considerations:

• Sirolimus.

• Nifedipine.

• Methotrexate.

• Potassium-sparing diuretics.

• NSAIDs (Naproxen, Sulindac).

• Immunosuppressive agents and radiation in psoriasis treatment.

Specific Considerations:

• Carcinogenesis, Mutagenesis, and Impairment of Fertility: Cyclosporine, a Pregnancy Category C drug, showed potential reproductive toxicity in animal studies. Malignancy risk increases with immunosuppression. Psoriasis patients on Cyclosporine reported malignancies, emphasizing the need for caution.

• Pregnancy: Cyclosporine poses risks in animal studies, and limited human data suggest potential adverse effects on pregnancy outcomes. The decision to use Cyclosporine during pregnancy should weigh the risks and benefits carefully.

• Nursing Mothers: Cyclosporine is detectable in breast milk. Because of the adverse reactions in breastfeeding infants (breastfeeding), discontinuation of nursing or the drug should be considered.

• Pediatric Use: Although used in transplant recipients as young as one year, the safety and effectiveness of Cyclosporine in individuals under the age of 18 with juvenile rheumatoid arthritis or psoriasis have not been established.

• Geriatric Use: Elderly patients (65 and older) may exhibit hypertension and serum creatinine rises. Dose selection should be cautious, considering potential organ function declines and comorbidities.