mph Bangladesh


Ciclosporin (US,Cyclosporine)

(sye' kloe spor een)

PCaution when used during lactation / LCI : Caution - pregnancy; Contraindication - lactation (breast feeding)

Molecule Info

 | See TERMINOLOGY & ABBREVIATIONS |
WARNING

Only physicians experienced in management of systemic immunosuppressive therapy for the indicated disease should prescribe Cyclosporine Capsules USP (Modified). At doses used in solid organ transplantation, only physicians experienced in immunosuppressive therapy and management of organ transplant recipients should prescribe Cyclosporine Capsules USP (Modified). Patients receiving the drug should be managed in facilities equipped and staffed with adequate laboratory and supportive medical resources. The physician responsible for maintenance therapy should have complete information requisite for the follow-up of the patient.

 

Cyclosporine Capsules USP (Modified), a systemic immunosuppressant, may increase the susceptibility to infection and the development of neoplasia. In kidney, liver, and heart transplant patients, Cyclosporine Capsules USP (Modified) may be administered with other immunosuppressive agents. Increased susceptibility to infection and the possible development of lymphoma and other neoplasms may result from the increase in the degree of immunosuppression in transplant patients.

 

Cyclosporine Capsules USP (Modified) and Cyclosporine Oral Solution USP (Modified) have increased bioavailability in comparison to Sandimmune® Soft Gelatin Capsules (cyclosporine capsules, USP). Cyclosporine Capsules USP (Modified) and Sandimmune® are not bioequivalent and cannot be used interchangeably without physician supervision. For a given trough concentration, cyclosporine exposure will be greater with Cyclosporine Capsules USP (Modified) than with Sandimmune®. If a patient who is receiving exceptionally high doses of Sandimmune® is converted to Cyclosporine Capsules USP (Modified), particular caution should be exercised. Cyclosporine blood concentrations should be monitored in transplant and rheumatoid arthritis patients taking Cyclosporine Capsules USP (Modified) to avoid toxicity due to high concentrations. Dose adjustments should be made in transplant patients to minimize possible organ rejection due to low concentrations. Comparison of blood concentrations in the published literature with blood concentrations obtained using current assays must be done with detailed knowledge of the assay methods employed.

For Psoriasis Patients

Psoriasis patients previously treated with PUVA and to a lesser extent, methotrexate or other immunosuppressive agents, UVB, coal tar, or radiation therapy, are at an increased risk of developing skin malignancies when taking Cyclosporine Capsules USP (Modified).

Cyclosporine, the active ingredient in Cyclosporine Capsules USP (Modified), in recommended dosages, can cause systemic hypertension and nephrotoxicity. The risk increases with increasing dose and duration of cyclosporine therapy. Renal dysfunction, including structural kidney damage, is a potential consequence of cyclosporine, and therefore, renal function must be monitored during therapy.

Indication(s) & Dosage

Transplantation indications

Organ transplantation

Prevention of graft rejection following kidney, liver, heart, combined heart-lung, lung or pancreas transplants.

Treatment of transplant rejection in patients previously receiving other immunosuppressive agents.

Bone marrow transplantation

Prevention of graft rejection following bone marrow transplantation and prophylaxis of graft-versus-host disease (GVHD).

Treatment of established graft-versus-host disease (GVHD).

Non-transplantation indications

Psoriasis

Cyclosporine Soft Gelatin Capsules and Cyclosporine Oral Solution are indicated in patients with severe psoriasis in whom conventional therapy is ineffective or inappropriate.

Atopic dermatitis

Cyclosporine Soft Gelatin Capsules and Cyclosporine Oral Solution are indicated for the short term treatment (8 weeks) of patients with severe atopic dermatitis in whom conventional therapy is ineffective or inappropriate.

Rheumatoid arthritis

Cyclosporine Soft Gelatin Capsules and Cyclosporine Oral Solution are indicated for the treatment of severe, active rheumatoid arthritis in patients in whom classical, slow-acting anti-rheumatic agents are inappropriate or ineffective.

Nephrotic syndrome

Cyclosporine Soft Gelatin Capsules and Cyclosporine Oral Solution are indicated for the treatment of steroid dependent or steroid resistant nephrotic syndrome (associated with adverse prognostic features) due to minimal change glomerulonephritis, focal segmental glomerulosclerosis or membranous glomerulonephritis in both adults and children.

Dosage & Administration

Dosage

Following initiation of treatment with Cyclosporine, due to the different bioavailabilities of the different oral ciclosporin formulations, patients should not be transferred to any other oral formulation of ciclosporin without appropriate monitoring of ciclosporin blood concentrations, serum creatinine levels and blood pressure. This does not apply to the conversion between Cyclosporine Soft Gelatin Capsules and Cyclosporine Oral Solution as these two forms are bioequivalent.

Due to the differences in bioavailability between different oral formulations of ciclosporin, it is important that prescribers, pharmacists and patients be aware that substitution of Cyclosporine with any other oral formulation of ciclosporin is not recommended as this may lead to alterations in ciclosporin blood levels. For this reason it may be appropriate to prescribe by brand.

Transplantation indications

Organ transplantation

Treatment with Cyclosporine Soft Gelatin Capsules or Cyclosporine Oral Solution should be initiated within 12 hours before transplantation at a dose of 10 to 15mg/kg body weight given in two divided doses.

As a general rule, treatment should continue at a dose of 10 to 15mg/kg per day given in two divided doses for one to two weeks post-operatively. Dosage should then be gradually reduced until a maintenance dose of about 2 to 6mg/kg per day is reached. This total daily dose should be given in two divided doses. Dosage should be adjusted by monitoring ciclosporin trough levels and kidney function.

When Cyclosporine is given with other immunosuppressants (e.g. with corticosteroids or as part of a triple or quadruple drug therapy), lower doses (e.g. 3 to 6mg/kg per day given orally in two divided doses) may be used for the initial treatment. For trough level monitoring, whole blood is preferred, measured by a specific analytical method. Target trough concentration ranges depend on organ type, time after transplantation and immunosuppressive regimen.

The use of SANDIMMUN Concentrate for Solution for Infusion is recommended only in organ transplant patients who are unable to take SANDIMMUN/Cyclosporine orally (e.g. shortly after surgery) or in whom the absorption of the oral forms might be impaired such as during episodes of gastrointestinal disturbances. It is recommended, however, that patients be transferred to Cyclosporine therapy as soon as the given circumstances allow (please refer to SANDIMMUN data sheet/SmPC for prescribing information on SANDIMMUN Concentrate for Solution for Infusion).

Bone marrow transplantation/prevention and treatment of graft-versus-host-disease (GVHD)

SANDIMMUN Concentrate for Solution for Infusion is usually preferred for initiation of therapy, although Cyclosporine Soft Gelatin Capsules or Cyclosporine Oral Solution may be used (please refer to SANDIMMUN data sheet/SmPC for prescribing information on SANDIMMUN Concentrate for Solution for Infusion).

Maintenance treatment should continue using Cyclosporine Soft Gelatin Capsules or Cyclosporine Oral Solution at a dosage of 12.5mg/kg per day, given in two divided doses, for at least three and preferably six months before tailing off to zero. In some cases it may not be possible to withdraw Cyclosporine until a year after bone marrow transplantation. Higher doses of Cyclosporine or the use of SANDIMMUN Concentrate for Solution for Infusion may be necessary in the presence of gastro-intestinal disturbances which might decrease absorption.

If Cyclosporine Soft Gelatin Capsules or Cyclosporine Oral Solution are used to initiate therapy, the recommended dose is 12.5 to 15mg/kg per day, given in two divided doses, starting on the day before transplantation.

If GVHD develops after Cyclosporine is withdrawn it should respond to reinstitution of therapy. Low doses of Cyclosporine should be used for mild, chronic GVHD.

Non-transplantation indications

Psoriasis

Due to the variability of this condition, treatment must be individualised. To induce remission, the recommended initial dose of Cyclosporine is 2.5mg/kg a day given orally in two divided doses. If there is no improvement after 1 month, the daily dose may be gradually increased, but should not exceed 5mg/kg. Treatment should be discontinued if sufficient response is not achieved within 6 weeks on a daily basis of 5mg/kg per day, or if the effective dose is not compatible with the safety guidelines given below. Initial doses of 5mg/kg per day of Cyclosporine are justified in patients whose condition requires rapid improvement.

For maintenance treatment, Cyclosporine dosage must be individually titrated to the lowest effective level, and the dosage should not exceed 5mg/kg per day, given orally in two divided doses.

Some clinical data are available which provide evidence that once satisfactory response is achieved, Cyclosporine may be discontinued and subsequent relapse managed with re-introduction of Cyclosporine at the previous effective dose. In some patients continuous maintenance therapy may be necessary.

Atopic dermatitis

The recommended dose range for Cyclosporine is 2.5-5mg/kg per day given orally in two divided doses for a maximum of 8 weeks. If a starting dose of 2.5mg/kg/day does not achieve a good initial response within 2 weeks the dose may be rapidly increased to a maximum of 5mg/kg per day. In very severe cases rapid and adequate control of disease is more likely with a starting dose of 5mg/kg per day, given orally in two divided doses.

Rheumatoid arthritis

It is recommended that initiation of Cyclosporine therapy should take place over a period of 12 weeks. For the first 6 weeks of treatment, the recommended dose is 2.5mg/kg per day, given orally in two divided doses. If the clinical effect is considered insufficient, the daily dose may be increased gradually as tolerability permits, but should not exceed 4mg/kg per day.

If, after 3 months of treatment at the maximum permitted or tolerable dose the response is considered inadequate, treatment should be discontinued.

For maintenance treatment the dose has to be titrated individually according to tolerability.

Cyclosporine can be given in combination with low-dose corticosteroids. Pharmacodynamic interactions can occur between ciclosporin and NSAIDs and therefore this combination should be used with care.

Long-term data on the use of ciclosporin in the treatment of rheumatoid arthritis are still limited. Therefore, it is recommended that patients are re-evaluated after 6 months of maintenance treatment and therapy only continued if the benefits of treatment outweigh the risks.

Nephrotic syndrome

To induce remission, the recommended dose is 5mg/kg per day given orally in two divided doses for adults and 6mg/kg per day given orally in two divided doses for children if, with the exception of proteinuria, renal function is normal. In patients with impaired renal function, the initial dose should not exceed 2.5mg/kg per day orally.

In focal segmental glomerulosclerosis, the combination of Cyclosporine and low dose corticosteroids may be of benefit.

In the absence of efficacy after 3 months treatment for minimal change glomerulonephritis and focal segmental glomerulosclerosis or 6 months treatment for membranous glomerulonephritis, Cyclosporine therapy should be discontinued.

For maintenance treatment the maximum recommended dose is 5mg/kg per day orally in adults or 6mg/kg per day orally in children. The doses need to be slowly reduced individually according to efficacy (proteinuria) and safety (primarily serum creatinine), to the lowest effective level.

Long-term data of ciclosporin in the treatment of nephrotic syndrome are limited. However, in clinical trials patients have received treatment for 1 to 2 years. Long-term treatment may be considered if there has been a significant reduction in proteinuria with preservation of creatinine clearance and provided adequate precautions are taken.

Administration

The total daily dosage of Cyclosporine Soft Gelatin Capsules or Cyclosporine Oral Solution should always be given in two divided doses. Cyclosporine Soft Gelatin Capsules should be taken with a mouthful of water and should then be swallowed whole.

Cyclosporine Oral Solution should be diluted immediately before being taken. For improved taste the solution can be diluted with orange juice or squash or apple juice. However, it may also be taken with water if preferred. It should be stirred well.

Cyclosporine Oral Solution has a characteristic taste which is distinct to that of SANDIMMUN Oral Solution.

The measuring device should not come into contact with the diluent. The measuring device should not be rinsed with water, alcohol or any other liquid. If it is necessary to clean the measuring device, the outside should be wiped with a dry tissue.

Owing to its possible interference with the P450-dependent enzyme system, grapefruit or grapefruit juice should not be ingested for 1 hour prior to dose administration, and grapefruit juice should not be used as a diluent for the Oral Solution.

Use in the Elderly

Experience with Cyclosporine in the elderly is limited. However, no particular problems have been reported following the use of ciclosporin at the recommended dose. Factors sometimes associated with ageing, in particular impaired renal function, make careful supervision essential and may necessitate dosage adjustment.

In rheumatoid arthritis clinical trials with ciclosporin, 17.5% of patients were aged 65 or older. These patients were more likely to develop systolic hypertension on therapy, and more likely to show serum creatinine rises ≥ 50% above the baseline after 3-4 months of therapy.

Clinical studies of Cyclosporine in transplant and psoriasis patients did not include a sufficient number of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experiences have not identified differences in response 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.

Use in Children

There is currently no experience with Cyclosporine in young children. However, transplant recipients from three months of age have received ciclosporin at the recommended dosage with no particular problems although at dosages above the upper end of the recommended range children seem to be more susceptible to fluid retention, convulsions and hypertension. This responds to dosage reduction.

Overdosage

The oral LD50 of ciclosporin is 2,329 mg/kg in mice, 1,480 mg/kg in rats and > 1,000 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.

Symptoms

Experience with acute overdosage of ciclosporin is limited . Oral doses of ciclosporin of 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 ciclosporin in premature neonates.

Treatment

In all cases of overdosage, general supportive measures should be followed and symptomatic treatment applied. Forced emesis and gastric lavage may be of value within the first few hours after oral intake. Signs of nephrotoxicity might occur which should be expected to resolve following drug withdrawal. Ciclosporin is not dialysable to any great extent nor is it well cleared by charcoal haemoperfusion. Hypertension and convulsions have been reported in some patients receiving ciclosporin therapy at doses above the recommended range and in others with high trough blood levels of ciclosporin. This might therefore, be expected as a feature of overdosage.

Contraindications
  • Hypersensitivity to ciclosporin or to any of the other excipients of Cyclosporine formulation.
  • Cyclosporine is contraindicated in psoriatic and atopic dermatitis patients with abnormal renal function, uncontrolled hypertension, uncontrolled infections or any kind of malignancy other than that of the skin.
  • Cyclosporine is contraindicated in rheumatoid arthritis patients with abnormal renal function, uncontrolled hypertension, uncontrolled infections or any kind of malignancy.
  • Cyclosporine should not be used to treat rheumatoid arthritis in patients under the age of 18 years.
  • Cyclosporine is contraindicated in nephrotic syndrome patients with uncontrolled hypertension, uncontrolled infections, or any kind of malignancy.
  • Concomitant use of tacrolimus & rosuvastatin is specifically contraindicated.
Special Precautions Renal and hepatic impairment; hyperuricaemia; anaphylaxis; history of allergic reactions; pregnancy; monitor BP, serum electrolytes, renal and hepatic function.
Adverse Drug Reaction(s) Hypertension; hepatoxicity; tremor; paraesthesia, hypertrichosis, facial oedema, acne; gingival hypertrophy; hyperkalaemia, fluid retention; increased susceptibility to infections; GI symptoms.
Potentially Fatal: Nephrotoxicity; convulsions.
Drug Interactions

Food interactions 

The concomitant intake of grapefruit juice has been reported to increase the bioavailability of ciclosporin.

Drug interactions

Of the many drugs reported to interact with ciclosporin, those for which the interactions are adequately substantiated and considered to have clinical implications are listed below.

Various agents are known to either increase or decrease plasma or whole blood ciclosporin levels usually by inhibition or induction of enzymes involved in the metabolism of ciclosporin, in particular CYP3A4. Ciclosporin is also an inhibitor of CYP3A4 and of the multidrug efflux transporter P-glycoprotein and may increase plasma levels of comedications that are substrates of this enzyme and/or transporter.

Drugs that decrease ciclosporin levels:

Barbiturates, carbamazepine, oxcarbazepine, phenytoin; nafcillin, sulfadimidine i.v.; rifampicin, octreotide, probucol, orlistat, hypericum perforatum (St John's Wort), ticlopidine, sulfinpyrazone, terbinafine, bosentan.

Drugs that increase ciclosporin levels:

Macrolide antibiotics (e.g. erythromycin, azithromycin and clarithromycin); ketoconazole, fluconazole, itraconazole, voriconazole; diltiazem, nicardipine, verapamil; metoclopramide; oral contraceptives; danazol; methylprednisolone (high dose); allopurinol; amiodarone; cholic acid and derivatives; protease inhibitors, imatinib; colchicines; nefazodone.

Other relevant drug interactions

Care should be taken when using ciclosporin together with other drugs that exhibit nephrotoxic synergy such as: aminoglycosides (including gentamicin, tobramycin), amphotericin B, ciprofloxacin, vancomycin, trimethoprim (+ sulfamethoxazole); non-steroidal anti-inflammatory drugs (including diclofenac, naproxen, sulindac); melphalan, histamine H2-receptor antagonists (e.g. cimetidine, ranitidine); methotrexate.

Concomitant use with tacrolimus should be avoided due to increased potential for nephrotoxicity.

The concurrent administration of nifedipine with ciclosporin may result in an increased rate of gingival hyperplasia compared with that observed when ciclosporin is given alone.

Following concomitant administration of ciclosporin and lercanidipine, the AUC of lercanidipine was increased threefold and the AUC of ciclosporin was increased 21%. Therefore caution is recommended when co-administering ciclosporin together with lercanidipine.

Ciclosporin is a highly potent Pgp inhibitor and may increase blood levels of concomitant medications that are substrates of Pgp such as aliskiren. Following concomitant administration of ciclosporin and aliskiren, the Cmax of aliskiren was increased by approximately 2.5 fold and the AUC by approximately 5 fold. However, the pharmacokinetic profile of ciclosporin was not significantly altered. Caution is recommended when co-administering ciclosporin together with aliskiren.

The concomitant use of diclofenac and ciclosporin has been found to result in a significant increase in the bioavailability of diclofenac, with the possible consequence of reversible renal function impairment. The increase in the bioavailability of diclofenac is most probably caused by a reduction of its first-pass effect. If non-steroidal anti-inflammatory drugs with a low first-pass effect (e.g. acetylsalicylic acid) are given together with ciclosporin, no increase in their bioavailability is to be expected.

Ciclosporin may reduce the clearance of digoxin, colchicine, prednisolone, HMG-CoA reductase inhibitors (statins) and etoposide.

Severe digitalis toxicity has been seen within days of starting ciclosporin in several patients taking digoxin. There are also reports on the potential of ciclosporin to enhance the toxic effects of colchicine such as myopathy and neuropathy, especially in patients with renal dysfunction. If digoxin or colchicine is used concurrently with ciclosporin, close clinical observation is required in order to enable early detection of toxic manifestations of digoxin or colchicine, followed by reduction of dosage or its withdrawal.

Literature and post marketing cases of myotoxicity, including muscle pain and weakness, myositis, and rhabdomyolysis, have been reported with concomitant administration of ciclosporin with lovastatin, simvastatin, atorvastatin, pravastatin, and rarely, fluvastatin. When concurrently administered with ciclosporin, 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. Rosuvastatin is specifically contraindicated with ciclosporin.

Elevations in serum creatinine were observed in the studies using everolimus or sirolimus in combination with full-dose ciclosporin for microemulsion. This effect is often reversible with ciclosporin dose reduction. Everolimus and sirolimus had only a minor influence on ciclosporin pharmacokinetics. Co-administration of ciclosporin significantly increases blood levels of everolimus and sirolimus.

Caution is required for concomitant use of potassium sparing drugs (e.g. potassium sparing diuretics, angiotensin converting enzyme inhibitors, angiotensin II receptor antagonists) or potassium containing drugs since they may lead to significant increases in serum potassium.

Ciclosporin may increase the plasma concentrations of repaglinide and thereby increase the risk of hypoglycaemia.

Recommendations

If the concomitant use of drug known to interact with ciclosporin cannot be avoided, the following basic recommendations should be observed.

During the concomitant use of a drug that may exhibit nephrotoxic synergy, close monitoring of renal function (in particular serum creatinine) should be performed. If a significant impairment of renal function occurs, the dosage of the co-administered drug should be reduced or alternative treatment considered.

In graft recipients there have been isolated reports of considerable but reversible impairment of kidney function (with corresponding increase in serum creatinine) following concomitant administration of fibric acid derivatives (e.g. bezafibrate, fenofibrate). Kidney function must therefore be closely monitored in these patients. In the event of significant impairment of kidney function the co-medication should be withdrawn.

Drugs known to reduce or increase the bioavailability of ciclosporin: in transplant patients frequent measurement of ciclosporin levels and, if necessary, ciclosporin dosage adjustment is required, particularly during the introduction or withdrawal of the co-administered drug. In non-transplant patients the value of ciclosporin blood level monitoring is questionable, as in these patients the relationship between blood level and clinical effect is less well established. If drugs known to increase ciclosporin levels are given concomitantly, frequent assessment of renal function and careful monitoring for ciclosporin related side-effects may be more appropriate than blood level measurement.

The concomitant use of nifedipine should be avoided in patients in whom gingival hyperplasia develops as a side effect of ciclosporin.

Non-steroidal anti-inflammatory drugs known to undergo strong first-pass metabolism (e.g. diclofenac) should be given at doses lower than those that would be used in patients not receiving ciclosporin. When diclofenac is given concomitantly with ciclosporin the dose of diclofenac should be reduced by approximately half.

If digoxin, colchicine or HMG-CoA reductase inhibitors (statins) are used concurrently with ciclosporin, close clinical observation is required in order to enable early detection of toxic manifestations of the drugs, followed by reduction of its dosage or its withdrawal. Please consult manufacturer's PI for detailed information before prescribing.

Use in Pregnancy

Pregnancy

Animal studies have shown reproductive toxicity in rats and rabbits.

Experience with Ciclosporin/Cyclosporine in pregnant women is limited. Pregnant women receiving immunosuppressive therapies after transplantation, including ciclosporin and ciclosporin containing regimens, are at risk of premature delivery (<37 weeks).

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

However there are no adequate and well controlled studies in pregnant women and, therefore Ciclosporin/Cyclosporine should not be used during pregnancy unless the potential benefit to the mother justifies the potential risk to the foetus.

Lactation

Ciclosporin passes into breast milk. Mothers receiving treatment with Ciclosporin/Cyclosporine should not breast-feed.

Storage Intravenous: Store at 25°C. Oral: Store at 25°C.
Pharmacology

Ciclosporin/Cyclosporine is a cyclic polypeptide consisting of 11 amino acids. It is a potent immunosuppressive agent which prolongs survival of allogeneic transplants involving skin, heart, kidney, pancreas, cornea, bone marrow, small intestine and lung in animals.

Successful solid organ and bone marrow allogeneic transplants have been performed in man, using ciclosporin to prevent and treat rejection and GVHD. Ciclosporin has been used both in Hepatitis C Virus (HCV) positive and HCV negative liver transplants recipients. Marked beneficial effects of ciclosporin therapy have also been shown in patients with severe psoriasis, atopic dermatitis, rheumatoid arthritis and nephrotic syndrome, conditions that may be considered to have an immunological mechanism.

Studies in animals suggest that ciclosporin inhibits the development of cell mediated reactions. It appears to block the resting lymphocytes in the G0 or early G1 phase of the cell cycle, and also inhibits lymphokine production and release, including interleukin 2 (T cell growth factor, TCGF). The available evidence suggests that ciclosporin acts specifically and reversibly on lymphocytes. It does not depress haemopoiesis and has no effect on the function of phagocytic cells.

Ciclosporin is a strong immunosuppressant that acts mainly on the helper T-cells. It inhibits the activation of calcineurin and production of interleukin-2, thus reducing cell-mediated immune response.
Absorption: Incompletely and variably absorbed from the GI tract (oral).
Distribution: Widely distributed; crosses the placenta and enters breast milk. Protein-binding: 90%.
Metabolism: Hepatic: Extensive.
Excretion: In faeces via the bile; 5-20 hr (elimination half-life), more rapid in children.

ATC Classification S01XA18 - ciclosporin; 
L04AD01 - ciclosporin;

Brand/Product Info


Total Products : 4    
Brand Name Manufacturer/Marketer Composition Dosage Form Pack Size & Price
CYCLORIN IBN SINA Pharmaceutical Industry Ltd. Cyclosporine USP 0.05% w/v Eye Drop 5ml: 210.00 MRP
CYPORIN Aristopharma Ltd. Cyclosporine USP 0.05% w/v Eye Drop 5ml: 210.00 MRP
NEORAL Novartis (Bangladesh) Ltd. Ciclosporin 25mg, 50mg & 100mg Capsule 50's each: 2,950.00; 5,850.00 & 11,700.00 MRP
SPORIUM Incepta Pharmaceuticals Limited Ciclosporin USP 100mg/ml Solution 50ml, MRP 2385.00

Gen. MedInfo

IMPORTANT WARNING:

Cyclosporine is available in its original form and as another product that has been modified (changed) so that the medication can be better absorbed in the body. Original cyclosporine and cyclosporine (modified) are absorbed by the body in different amounts, so they cannot be substituted for one another. Take only the type of cyclosporine that was prescribed by your doctor. When your doctor gives you a written prescription, check to be sure that he or she has specified the type of cyclosporine you should receive. Each time you have your prescription filled, look at the brand name printed on your prescription label to be sure that you have received the same type of cyclosporine. Talk to your pharmacist if the brand name is unfamiliar or you are not sure you have received the right type of cyclosporine.

Taking cyclosporine or cyclosporine (modified) may increase the risk that you will develop an infection or cancer, especially lymphoma (cancer of a part of the immune system) or skin cancer. This risk may be higher if you take cyclosporine or cyclosporine (modified) with other medications that decrease the functioning of the immune system such as azathioprine (Imuran), cancer chemotherapy, methotrexate (Rheumatrex), sirolimus (Rapamune), and tacrolimus (Prograf). Tell your doctor if you are taking any of these medications, and if you have or have ever had any type of cancer. To reduce your risk of skin cancer, plan to avoid unnecessary or prolonged exposure to sunlight and to wear protective clothing, sunglasses, and sunscreen during your treatment. If you experience any of the following symptoms, call your doctor immediately: sore throat, fever, chills, and other signs of infection; flu-like symptoms; coughing; difficulty urinating; pain when urinating; a red, raised, or swollen area on the skin; new sores or discoloration on the skin; lumps or masses anywhere in your body; night sweats; swollen glands in the neck, armpits, or groin; trouble breathing; chest pain; weakness or tiredness that does not go away; or pain, swelling, or fullness in the stomach.

Cyclosporine and cyclosporine (modified) may cause high blood pressure and kidney damage. Tell your doctor if you have or have ever had high blood pressure or kidney disease. Also tell your doctor if you are taking any of the following medications: amphotericin B; cimetidine; ciprofloxacin; colchicine; fenofibrate; gemfibrozil; gentamicin; ketoconazole (Nizoral); melphalan; nonsteroidal anti-inflammatory drugs such as diclofenac (Cataflam, Voltaren), naproxen (Aleve, Naprosyn), and sulindac; ranitidine (Zantac); tobramycin; trimethoprim with sulfamethoxazole; and vancomycin. If you experience any of the following symptoms, call your doctor immediately: dizziness; swelling of the arms, hands, feet, ankles, or lower legs; fast, shallow breathing; nausea; or irregular heartbeat.

If you have psoriasis, tell your doctor about all the psoriasis treatments and medications you are using or have used in the past. The risk that you will develop skin cancer is greater if you have ever been treated with PUVA (psoralen and UVA; treatment for psoriasis that combines an oral or topical medication with exposure to ultraviolet A light); methotrexate (Rheumatrex) or other medications that suppress the immune system; UVB (exposure to ultraviolet B light to treat psoriasis); coal tar; or radiation therapy. You should not be treated with PUVA, UVB, or medications that suppress the immune system while you are taking cyclosporine (modified) to treat psoriasis.

Keep all appointments with your doctor and the laboratory. Your doctor will order certain lab tests to check your body's response to cyclosporine or cyclosporine (modified).

 

Why is cyclosporine prescribed?

Cyclosporine and cyclosporine (modified) are used with other medications to prevent transplant rejection (attack of the transplanted organ by the immune system of the person who received the organ) in people who have received kidney, liver, and heart transplants. Cyclosporine (modified) is also used alone or with methotrexate (Rheumatrex) to treat the symptoms of rheumatoid arthritis (arthritis caused by swelling of the lining of the joints) in patients whose symptoms were not relieved by methotrexate alone. Cyclosporine (modified) is also used to treat psoriasis (a skin disease in which red, scaly patches form on some areas of the body) in certain patients who have not been helped by other treatments. Cyclosporine and cyclosporine (modified) are in a class of medications called immunosuppressants. They work by decreasing the activity of the immune system.

How should cyclosporine be used?

Cyclosporine and cyclosporine (modified) both come as a capsule and a solution (liquid) to take by mouth. Cyclosporine is usually taken once a day. Cyclosporine (modified) is usually taken twice a day. It is important to take both types of cyclosporine on a regular schedule. Take cyclosporine or cyclosporine (modified) at the same time(s) each day, and allow the same amount of time between doses and meals every day. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take cyclosporine or cyclosporine (modified) exactly as directed. Do not take more or less of the medication or take it more often than prescribed by your doctor.

Your doctor will probably adjust your dose of cyclosporine or cyclosporine (modified) during your treatment. If you are taking either type of cyclosporine to prevent transplant rejection, your doctor will probably start you on a high dose of the medication and gradually decrease your dose. If you are taking cyclosporine (modified) to treat rheumatoid arthritis or psoriasis, your doctor will probably start you on a low dose of the medication and gradually increase your dose. Your doctor may also decrease your dose if you experience side effects of the medication. Tell your doctor how you are feeling during your treatment.

Cyclosporine (modified) helps control the symptoms of psoriasis and rheumatoid arthritis, but does not cure these conditions. If you are taking cyclosporine (modified) to treat psoriasis, it may take 2 weeks or longer for your symptoms to begin to improve, and 12 to 16 weeks for you to feel the full benefit of the medication. If you are taking cyclosporine (modified) to treat rheumatoid arthritis, it may take 4 to 8 weeks for your symptoms to improve. Continue to take cyclosporine (modified) even if you feel well. Do not stop taking cyclosporine (modified) without talking to your doctor. Your doctor may decrease your dose gradually.

You may notice an unusual smell when you open a blister card of cyclosporine capsules. This is normal and does not mean that the medication is damaged or unsafe to use.

Cyclosporine (modified) oral solution may gel or become lumpy if it is exposed to temperatures below 68 °F (20 °C). You can use the solution even if it has gelled, or you can turn the solution back to a liquid by allowing it to warm to room temperature (77 °F [25 °C]).

Cyclosporine and cyclosporine (modified) oral solution must be mixed with a liquid before use. Cyclosporine (modified) oral solution may be mixed with orange juice or apple juice but should not be mixed with milk. Cyclosporine oral solution may be mixed with milk, chocolate milk, or orange juice. You should choose one drink from the appropriate list and always mix your medication with that drink.

To take either type of oral solution, follow these steps:

  • Fill a glass (not plastic) cup with the drink you have chosen.

  • Remove the protective cover from the top of the dosing syringe that came with your medication.

  • Place the tip of the syringe into the bottle of solution and pull back on the plunger to fill the syringe with the amount of solution your doctor has prescribed.

  • Hold the syringe over the liquid in your glass and press down on the plunger to place the medication in the glass.

  • Stir the mixture well.

  • Drink all of the liquid in the glass right away.

  • Pour a little more of the drink you have chosen into the glass, swirl the glass around to rinse, and drink the liquid.

  • Dry the outside of the syringe with a clean towel and replace the protective cover. Do not wash the syringe with water. If you do need to wash the syringe, be sure that it is completely dry before you use it to measure another dose.

Other uses for cyclosporine

Cyclosporine and cyclosporine (modified) are also sometimes used to treat Crohn's disease (a condition in which the body attacks the lining of the digestive tract, causing pain, diarrhea, weight loss, and fever) and to prevent rejection in patients who have received pancreas or cornea transplants. Talk to your doctor about the possible risks of using cyclosporine for your condition.

This medication may be prescribed for other uses. Ask your doctor or pharmacist for more information.

What special precautions should I follow?

 Before taking Cyclosporine or cyclosporine (modified),
  • tell your doctor if you are allergic to cyclosporine, cyclosporine (modified), any other medications, or any of the inactive ingredients in cyclosporine or cyclosporine (modified) capsules or solution. Ask your pharmacist for a list of the inactive ingredients.
  • tell your doctor what prescription and nonprescription medications, vitamins, and nutritional supplements you are taking, or plan to take. Be sure to mention the medications listed in the IMPORTANT WARNING section and any of the following: acyclovir; allopurinol; amiodarone; angiotensin-converting enzyme  inhibitors such as benazepril, captopril, enalapril, fosinopril, lisinopril, moexipril, perindopril, quinapril, ramipril, and trandolapril; angiotensin II receptor antagonists such as candesartan, eprosartan, irbesartan, losartan, olmesartan, telmisartan, and valsartan; certain antifungal medications such as fluconazole, and itraconazole; azithromycin; bromocriptine; calcium channel blockers such as diltiazem, nicardipine, and verapamil; carbamazepine; cholesterol-lowering medications  such as atorvastatin, fluvastatin, lovastatin, pravastatin, and simvastatin; clarithromycin; dalfopristin and quinupristin combination; danazol; digoxin; certain diuretics  including amiloride, spironolactone, and triamterene; erythromycin; HIV protease inhibitors such as indinavir, nelfinavir, ritonavir, and saquinavir; imatinib; metoclopramide; methylprednisolone; nafcillin; octreotide; oral contraceptives; orlistat; phenobarbital; phenytoin; potassium supplements; prednisolone; repaglinide; rifabutin; rifampin; sulfinpyrazone; terbinafine; and ticlopidine . Your doctor may need to change the doses of your medications or monitor you more carefully for side effects.
  • if you are taking sirolimus, take it 4 hours after you take cyclosporine or cyclosporine (modified).
  • tell your doctor what herbal products you are taking, especially St. John's wort.
  • tell your doctor if you have or have ever had any of the conditions mentioned in the IMPORTANT WARNING section or any of the following: low cholesterol, low levels of magnesium in your blood, any condition that makes it difficult for your body to absorb nutrients, or liver disease.
  • tell your doctor if you are pregnant or plan to become pregnant. If you become pregnant while taking either type of cyclosporine, call your doctor. Both types of cyclosporine may increase the risk that your baby will be born too early.
  • tell your doctor if you are breast-feeding or planning to breast-feed.
  • do not have vaccinations without talking to your doctor.
  • you should know that cyclosporine may cause growth of extra tissue in your gums. Be sure to brush your teeth carefully and see a dentist regularly during your treatment to decrease the risk that you will develop this side effect.

What special dietary instructions should I follow?

Avoid drinking grapefruit juice or eating grapefruit while taking Cyclosporine or cyclosporine (modified).

Your doctor may tell you to limit the amount of potassium in your diet. Follow these instructions carefully. Talk to your doctor about the amount of potassium-rich foods such as bananas, prunes, raisins, and orange juice you may have in your diet. Many salt substitutes contain potassium, so talk to your doctor about using them during your treatment.

What should I do if I forget a dose?

If you forget to take a dose, take the missed dose as soon as you remember it. However, if it is almost time for the next dose, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.

What side effects can cyclosporine cause?

Cyclosporine and cyclosporine (modified) may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:
  • headache

  • diarrhea

  • heartburn

  • gas

  • increased hair growth on the face, arms, or back

  • growth of extra tissue on the gums

  • acne

  • flushing

  • uncontrollable shaking of a part of your body

  • burning or tingling in the hands, arms, feet, or legs

  • muscle or joint pain

  • cramps

  • pain or pressure in the face

  • ear problems

  • breast enlargement in men

  • depression

  • difficulty falling asleep or staying asleep

 Some side effects can be serious. If you experience any of the following symptoms, or those listed in the IMPORTANT WARNING section, call your doctor immediately:

  • unusual bleeding or bruising

  • pale skin

  • yellowing of the skin or eyes

  • seizures

  • loss of consciousness

  • changes in behavior or mood

  • difficulty controlling body movements

  • changes in vision

  • confusion

  • rash

  • purple blotches on the skin

  • swelling of the hands, arms, feet, ankles, or lower legs

Cyclosporine and cyclosporine (modified) may cause other side effects. Talk to your doctor if you experience unusual problems while taking either medication.

What should I know about storage and disposal of cyclosporine?

Keep cyclosporine in the container it came in, tightly closed and out of reach of children. Store it at room temperature and away from excess heat and moisture (not in the bathroom). Do not store cyclosporine in the refrigerator and do not freeze it. Throw away any medication that is outdated or no longer needed. Throw away any remaining solution 2 months after you first open the bottle. Talk to your pharmacist about the proper disposal of your medication.

In case of emergency/overdose

In case of overdose, consult your doctor. If the victim has collapsed or is not breathing, consult local medical emergency services.

 Symptoms of overdose may include:

  • yellowing of the skin or eyes

  • swelling of the arms, hands, feet, ankles, or lower legs.

What other information should I know?

Do not let anyone else take your medicine. 

It is important for you to keep a written list of all of the prescription and nonprescription (over-the-counter) medicines you are taking, as well as any products such as vitamins, minerals, or other dietary supplements. You should bring this list with you each time you visit a doctor or if you are admitted to a hospital. It is also important information to carry with you in case of emergencies.

This medication may cause other side effects.  Consult your doctor if you have any unusual problems while taking this.

Ref:  MedlinePlus, U.S. National Library of Medicine.


This information is provided for reference only and not a replacement for and should only be used in conjunction with full consultation with a registered medical practitioner. It may not contain all the available information you require and cannot substitute professional medical care, nor does it take into account all individual circumstances. Although great effort has been made to ensure content accuracy, mph-bd shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions or otherwise.

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