Restasis (Allergan Inc)

Restasis (Allergan Inc) - General Information

A cyclic undecapeptide from an extract of soil fungi. It is a powerful immunosupressant with a specific action on T-lymphocytes. It is used for the prophylaxis of graft rejection in organ and tissue transplantation. (From Martindale, The Extra Pharmacopoeia, 30th ed).

Pharmacology of Restasis (Allergan Inc)

Used in immunosuppression for prophylactic treatment of organ transplants, cyclosporine exerts specific and reversible inhibition of immunocompetent lymphocytes in the G0-or G1-phase of the cell cycle. T-lymphocytes are preferentially inhibited. The T1-helper cell is the main target, although the T1-suppressor cell may also be suppressed. Sandimmune (cyclosporine) also inhibits lymphokine production and release including interleukin-2.

Restasis (Allergan Inc) for patients

The emulsion from one individual single-use vial is to be used immediately after opening for administration to one or both eyes, and the remaining contents should be discarded immediately after administration.

Do not allow the tip of the vial to touch the eye or any surface, as this may contaminate the emulsion.

RESTASIS™ should not be administered while wearing contact lenses. Patients with decreased tear production typically should not wear contact lenses. If contact lenses are worn, they should be removed prior to the administration of the emulsion. Lenses may be reinserted 15 minutes following administration of RESTASIS™ ophthalmic emulsion.

Restasis (Allergan Inc) Interactions

All of the individual drugs cited below are well substantiated to interact with cyclosporine. In addition, concomitant non-steroidal anti-inflammatory drugs, particularly in the setting of dehydration, may potentiate renal dysfunction.

Drugs That Alter Cyclosporine Concentrations:

Compounds that decrease cyclosporine absorption such as orlistat should be avoided. Cyclosporine is extensively metabolized by cytochrome P-450 3A. Substances that inhibit this enzyme could decrease metabolism and increase cyclosporine concentrations. Substances that are inducers of cytochrome P-450 activity could increase metabolism and decrease cyclosporine concentrations. Monitoring of circulating cyclosporine concentrations and appropriate Sandimmune^Ã? (cyclosporine) dosage adjustment are essential when these drugs are used concomitantly.

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

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

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

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

Nonsteroidal Anti-inflammatory Drug (NSAID) Interactions: Clinical status and serum creatinine should be closely monitored when cyclosporine is used with nonsteroidal antiinflammatory agents in rheumatoid arthritis patients.

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

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

Other Drug Interactions: Cyclosporine may reduce the clearance of digoxin, colchicine, prednisolone and HMG-CoA reductase inhibitors (statins). Severe digitalis toxicity has been seen within days of starting cyclosporine in several patients taking digoxin. There are also reports on the potential of cyclosporine to enhance the toxic effects of colchicine such as myopathy and neuropathy, especially in patients with renal dysfunction. If digoxin or colchicine are used concurrently with cyclosporine, close clinical observation is required in order to enable early detection of toxic manifestations of digoxin or colchicine, followed by reduction of dosage and its withdrawal.

Literature and postmarketing cases of myotoxicity, including muscle pain and weakness, myositis, and rhabdomyolysis, have been reported with concomitant administration of cyclosporine with lovastatin, simvastatin, atorvastatin, pravastatin, and rarely, fluvastatin. When concurrently administered with cyclosporine, the dosage of these statins should be reduced according to label recommendations. Statin therapy needs to be temporarily withheld or discontinued in patients with signs and symptoms of myopathy or those with risk factors predisposing to severe renal injury, including renal failure, secondary to rhabdomyolysis. Cyclosporine should not be used with potassium-sparing diuretics because hyperkalemia can occur. Caution is also required when cyclosporine is co-administered with potassium sparing drugs (e.g. angiotensin converting enzyme inhibitors, angiotensin II receptor antagonists), potassium containing drugs as well as in patients on a potassium rich diet. Control of potassium levels in these situations is advisable.

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

During treatment with cyclosporine, vaccination may be less effective. The use of live vaccines should be avoided. Frequent gingival hyperplasia with nifedipine, and convulsions with high dose methylprednisolone have been reported.

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

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

Restasis (Allergan Inc) Contraindications

RESTASIS™ is contraindicated in patients with active ocular infections and in patients with known or suspected hypersensitivity to any of the ingredients in the formulation.

Additional information about Restasis (Allergan Inc)

Restasis (Allergan Inc) Indication: For treatment of transplant rejection, rheumatoid arthritis, severe psoriasis
Mechanism Of Action: Restasis (Allergan Inc) binds to cyclophillin. The complex then inhibits calcineurin which is normally responsible for activating transcription of interleukin 2. Restasis (Allergan Inc) also inhibits lymphokine production and interleukin release. In ophthalmic applications, the precise mechanism of action is not known. Restasis (Allergan Inc) emulsion is thought to act as a partial immunomodulator in patients whose tear production is presumed to be suppressed due to ocular inflammation associated with keratoconjunctivitis sicca.
Drug Interactions: Acetazolamide Acetazolamide increases the effect and toxicity of cyclosporine
Allopurinol Allopurinol increases the effect and toxicity of cyclosporine
Methotrexate Increases the effect and toxicity of methotrexate
Amiodarone Amiodarone increases the effect and toxicity of cyclosporine
Amobarbital The barbiturate increases the effect of cyclosporine
Amphotericin B Monitor for nephrotoxicity
Amprenavir The protease inhibitor increases the effect of cyclosporine
Aprobarbital The barbiturate increases the effect of cyclosporine
Atazanavir Atazanavir increases the effect and toxicity of immunosuppressant
Atorvastatin Possible myopathy and rhabdomyolysis
Azithromycin The macrolide increases the effect of cyclosporine
Bosentan Increases the effect and toxicity of bosentan
Bupropion Bupropion decreases the effect of cyclosporine
Butabarbital The barbiturate increases the effect of cyclosporine
Butalbital The barbiturate increases the effect of cyclosporine
Butethal The barbiturate increases the effect of cyclosporine
Carbamazepine Carbamazepine decreases the effect of cyclosporine
Carvedilol Carvedilol increases the effect and toxicity of cyclosporine
Cerivastatin Possible myopathy and rhabdomyolysis
Chloramphenicol Chloramphenicol increases the effect of cyclosporine
Chloroquine Chloroquine increases the effect of cyclosporine
Ciprofloxacin The quinolone increases the effect and toxicity of cyclosporine
Clarithromycin The macrolide increases the effect of cyclosporine
Clindamycin Clindamycin decreases the effect of cyclosporine
Colchicine Increased toxicity of both drugs
Danazol The androgen increases the effect and toxicity of cyclosporine
Diclofenac Monitor for nephrotoxicity
Digoxin Increases the effect of digoxin
Dihydroquinidine barbiturate The barbiturate increases the effect of cyclosporine
Diltiazem Diltiazem increases the effect and toxicity of cyclosporine
Efavirenz Efavirenz decreases the levels of cyclosporine
Erythromycin The macrolide increases the effect of cyclosporine
Ethinyl Estradiol The contraceptive increases the effect and toxicity of cyclosporine
Ethotoin The hydantoin decreases the effect of cyclosporine
Etodolac Monitor for nephrotoxicity
Etoposide Increases the effect of etoposide
Ezetimibe Increases the effect and toxicity of ezetimibe
Fenoprofen Monitor for nephrotoxicity
Fluconazole Fluconazole increases the effect of the immunosuppressant
Fluoxetine The antidepressant increases the effect and toxicity of cyclosporine
Flurbiprofen Monitor for nephrotoxicity
Fluvastatin Possible myopathy and rhabdomyolysis
Fosamprenavir The protease inhibitor increases the effect of cyclosporine
Foscarnet Monitor for nephrotoxicity
Fosphenytoin The hydantoin decreases the effect of cyclosporine
Glimepiride The sulfonylurea increases the effect of cyclosporine
Glipizide The sulfonylurea increases the effect of cyclosporine
Griseofulvin Griseofulvin decreases the effect of cyclosporine
Heptabarbital The barbiturate increases the effect of cyclosporine
Hexobarbital The barbiturate increases the effect of cyclosporine
Ibuprofen Monitor for nephrotoxicity
Imatinib Imatinib increases the effect and toxicity of cyclosporine
Indinavir The protease inhibitor increases the effect of cyclosporine
Indomethacin Monitor for nephrotoxicity
Itraconazole The imidazole increases the effect of immunosuppressant
Josamycin The macrolide increases the effect of cyclosporine
Ketoconazole The imidazole increases the effect of immunosuppressant
Ketoprofen Monitor for nephrotoxicity
Lovastatin Possible myopathy and rhabdomyolysis
Meclofenamic acid Monitor for nephrotoxicity
Mefenamic acid Monitor for nephrotoxicity
Melphalan Melphalan increases toxicity of cyclosporine
Mephenytoin The hydantoin decreases the effect of cyclosporine
Mestranol The contraceptive increases the effect and toxicity of cyclosporine
Methohexital The barbiturate increases the effect of cyclosporine
Methylphenidate Methylphenidate increases the effect and toxicity of cyclosporine
Methylphenobarbital The barbiturate increases the effect of cyclosporine
Metoclopramide Metoclopramide increases serum levels of cyclosporine
Modafinil Modafinil decreases the effect of cyclosporine
Muromonab Muromonab increases the levels of cyclosporine
Nabumetone Monitor for nephrotoxicity
Nafcillin Nafcillin alters serum levels of cyclosporine
Naproxen Monitor for nephrotoxicity
Nefazodone The antidepressant increases the effect and toxicity of cyclosporine
Nelfinavir The protease inhibitor increases the effect of cyclosporine
Nicardipine Nicardipine increases the effect and toxicity of cyclosporine
Nifedipine Increased risk of gingivitis
Norfloxacin The quinolone increases the effect and toxicity of cyclosporine
Octreotide Octreotide decreases the effect of cyclosporine
Omeprazole Omeprazole increases the effect and toxicity of cyclosporine
Orlistat Orlistat decreases the effect of cyclosporine
Oxaprozin Monitor for nephrotoxicity
Oxcarbazepine Oxcarbazepine decreases the effect of cyclosporine
Pentobarbital The barbiturate increases the effect of cyclosporine
Phenobarbital The barbiturate increases the effect of cyclosporine
Phenytoin The hydantoin decreases the effect of cyclosporine
Piroxicam Monitor for nephrotoxicity
Posaconazole Increased level of cyclosporine
Pravastatin Possible myopathy and rhabdomyolysis
Primidone The barbiturate increases the effect of cyclosporine
Propafenone Propafenone increases the effect and toxicity of cyclosporine
Pyrazinamide Pyrazinamide decreases the effect of cyclosporine
Quinidine barbiturate The barbiturate increases the effect of cyclosporine
Quinupristin Synercid increases the effect of cyclosporine
Repaglinide Increases repaglinide's effect
Rifabutin The rifamycin decreases the effect of cyclosporine
Rifampin The rifamycin decreases the effect of cyclosporine
Ritonavir The protease inhibitor increases the effect of cyclosporine
Rosuvastatin Increases the effect and toxicity of rosuvastatin
Roxithromycin The macrolide increases the effect of cyclosporine
Saquinavir The protease inhibitor increases the effect of cyclosporine
Secobarbital The barbiturate increases the effect of cyclosporine
Sevelamer Sevelamer decreases the effect of cyclosporine
Sibutramine Sibutramine increases the effect and toxicity of cyclosporine
Simvastatin Possible myopathy and rhabdomyolysis
Sirolimus Increases the effect and toxicity of sirolimus
St. John's Wort St. John's Wort decreases the effect of cyclosporine
Sulfadiazine The sulfonamide decreases the effect of cyclosporine
Sulfamethoxazole The sulfonamide decreases the effect of cyclosporine
Sulfasalazine The sulfonamide decreases the effect of cyclosporine
Sulfinpyrazone Sulfinpyrazone decreases the effect of cyclosporine
Sulindac Monitor for nephrotoxicity
Tacrolimus Additive toxicities for these agents
Talbutal The sulfonamide decreases the effect of cyclosporine
Telithromycin Telithromycin may possibly increase this agent effect/toxicity
Tenoxicam Monitor for nephrotoxicity
Terbinafine Terbinafine decreases the effect of cyclosporine
Ticlopidine Ticlopidine decreases the effect of cyclosporine
Tolmetin Monitor for nephrotoxicity
Troglitazone Troglitazone decreases the effect of the immunosuppressant
Troleandomycin The macrolide increases the effect of cyclosporine
Verapamil Verapamil increases the effect of cyclosporine
Voriconazole Voriconazole increases the effect and toxicity of cyclosporine
Caspofungin Restasis (Allergan Inc) increases the effect and toxicity of caspofungin
Cilastatin Imipenem increases the effect and toxicity of cyclosporine
Imipenem Imipenem increases the effect and toxicity of cyclosporine
Glibenclamide The sulfonylurea increases the effect of cyclosporine
Probucol Probucol decreases the effect of cyclosporine
Sulfamethazine The sulfonamide decreases the effect of cyclosporine
Tiaprofenic acid Monitor for nephrotoxicity
Ursodeoxycholic acid Ursodiol increases the levels of cyclosporine
Food Interactions: Avoid salt substitutes containing potassium.
Avoid taking with grapefruit or grapefruit juice as grapefruit can significantly increase serum levels of this product.
Take without regard to meals.
Red wine may reduce cyclosporine levels due to increased metabolism, therefore it appears prudent to avoid red wine (white wine does not appear to affect cyclosporine metabolism).
Generic Name: Cyclosporine
Synonyms: Ciclosporin; Cyclosporin; Cyclosporin A
Drug Category: Immunomodulatory Agents; Immunosuppressive Agents; Antifungal Agents; Dermatologic Agents; Enzyme Inhibitors; Antirheumatic Agents
Drug Type: Biotech; Approved

Other Brand Names containing Cyclosporine: Gengraf (Abbott labs); Neoral (Novartis); Restasis (Allergan Inc); Sandimmune (Novartis); Sangcya;
Absorption: The absorption of cyclosporine from the gastrointestinal tract is incomplete and variable. Compared to an intravenous infusion, the absolute bioavailability of the oral solution is approximately 30% based upon the results in 2 patients.
Toxicity (Overdose): The oral LD₅₀ is 2329 mg/kg in mice, 1480 mg/kg in rats, and > 1000 mg/kg in rabbits. The I.V. LD₅₀ is 148 mg/kg in mice, 104 mg/kg in rats, and 46 mg/kg in rabbits.
Protein Binding: Approximately 90% is bound to proteins, primarily lipoproteins.
Biotransformation: Hepatic, extensively metabolized.
Half Life: Biphasic and variable, approximately 7 hours (range 7 to 19 hours) in children and approximately 19 hours (range 10 to 27 hours) in adults.
Dosage Forms of Restasis (Allergan Inc): Capsule Oral
Solution Oral
Liquid Intravenous
Chemical IUPAC Name: 30-ethyl-33-[(E,1R,2R)-1-hydroxy-2-methylhex-4-enyl]-1,4,7,10,12,15,19,25,28-nonamethyl-6,9,18,24-tetrakis(2-methylpropyl)-3,21-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29,32-undecone
Chemical Formula: C62H111N11O12
Cyclosporine on Wikipedia: https://en.wikipedia.org/wiki/Cyclosporine
Organisms Affected: Humans and other mammals