SandIMMUNE

There is a minimal experience with overdosage. Because of the slow absorption of Sandimmune Soft Gelatin Capsules or Oral Solution, forced emesis and gastric lavage would be of value up to 2 hours after administration. Transient hepatotoxicity and nephrotoxicity may occur which should resolve following drug withdrawal. Oral doses of cyclosporine up to 10 g (about 150 mg/kg) have been tolerated with relatively minor clinical consequences, such as vomiting, drowsiness, headache, tachycardia and, in a few patients, moderately severe, reversible impairment of renal function. However, serious symptoms of intoxication have been reported following accidental parenteral overdosage with cyclosporine in premature neonates. General supportive measures and symptomatic treatment should be followed in all cases of overdosage. Sandimmune (cyclosporine) is not dialyzable to any great extent, nor is it cleared well by charcoal hemoperfusion. The oral LD50 is 2329 mg/kg in mice, 1480 mg/kg in rats, and > 1000 mg/kg in rabbits. The intravenous (IV) LD50 is 148 mg/kg in mice, 104 mg/kg in rats, and 46 mg/kg in rabbits.

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

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

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

Tell your doctor about all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements. Especially tell your doctor if you take:

• other medications that decrease the functioning of the immune system such as azathioprine (Imuran), cancer chemotherapy, methotrexate (Rheumatrex), sirolimus (Rapamune), and tacrolimus (Prograf)
• other medicines that can cause high blood pressure or kidney damage such as amphotericin B (Amphotec, Fungizone); cimetidine (Tagamet); ciprofloxacin (Cipro); colchicine; fenofibrate (Antara, Lipophen, Tricor); gemfibrozil (Lopid); gentamicin; ketoconazole (Nizoral); melphalan (Alkeran); nonsteroidal anti-inflammatory drugs such as diclofenac (Cataflam, Voltaren), naproxen (Aleve, Naprosyn), and sulindac (Clinoril); ranitidine (Zantac); tobramycin (Tobi); trimethoprim with sulfamethoxazole (Bactrim, Septra); and vancomycin (Vancocin)
• acyclovir (Zovirax)
• allopurinol (Zyloprim)
• amiodarone (Cordarone)
• angiotensin-converting enzyme (ACE) inhibitors such as benazepril (Lotensin), captopril (Capoten), enalapril (Vasotec), fosinopril (Monopril), lisinopril (Prinivil, Zestril), moexipril (Univasc), perindopril (Aceon), quinapril (Accupril), ramipril (Altace), and trandolapril (Mavik)
• angiotensin II receptor antagonists such as candesartan (Atacand), eprosartan (Teveten), irbesartan (Avapro), losartan (Cozaar), olmesartan (Benicar), telmisartan (Micardis), and valsartan (Diovan)
• certain antifungal medications such as fluconazole (Diflucan), and itraconazole (Sporanox); azithromycin (Zithromax)
• bromocriptine (Parlodel)
• calcium channel blockers such as diltiazem (Cardizem), nicardipine (Cardene), and verapamil (Calan); carbamazepine (Tegretol)
• cholesterol-lowering medications (statins) such as atorvastatin (Lipitor), fluvastatin (Lescol), lovastatin (Mevacor), pravastatin (Pravachol), and simvastatin (Zocor)
• clarithromycin (Biaxin)
• dalfopristin and quinupristin combination (Synercid)
• danazol
• digoxin (Lanoxin)
• certain diuretics ('water pills') including amiloride (Midamor), spironolactone (Aldactone), and triamterene (Dyazide)
• erythromycin
• HIV protease inhibitors such as indinavir (Crixivan), nelfinavir (Viracept), ritonavir (Norvir, in Kaletra), and saquinavir (Fortovase)
• imatinib (Gleevec)
• metoclopramide (Reglan)
• methylprednisolone (Medrol)
• nafcillin; octreotide (Sandostatin)
• oral contraceptives (birth control pills)
• orlistat (Xenical)
• phenobarbital
• phenytoin (Dilantin)
• potassium supplements
• prednisolone (Pediapred)
• repaglinide (Prandin)
• rifabutin (Mycobutin)
• rifampin (Rifadin, Rimactane)
• St. John's wort
• sulfinpyrazone (Anturane)
• terbinafine (Lamisil)
• ticlopidine (Ticlid)

This is not a complete list of Sandimmune drug interactions. Ask your doctor or pharmacist for more information.

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

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies on the relationship of age to the effects of cyclosporine injection have not been performed in the pediatric population. However, no pediatric-specific problems have been documented to date.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of cyclosporine injection in the elderly. However, elderly patients are more likely to have high blood pressure or age-related kidney, liver, or heart problems, which may require caution and an adjustment in the dose for patients receiving cyclosporine injection.

Pregnancy

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are receiving this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Amifampridine
• Bosentan
• Colchicine
• Dronedarone
• Grazoprevir
• Lercanidipine
• Mifepristone
• Pitavastatin
• Simvastatin
• Sitaxsentan

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Aceclofenac
• Acemetacin
• Afatinib
• Alefacept
• Alfalfa
• Aliskiren
• Amlodipine
• Amtolmetin Guacil
• Aspirin
• Atorvastatin
• Bacillus of Calmette and Guerin Vaccine, Live
• Betrixaban
• Black Cohosh
• Blinatumomab
• Bromfenac
• Bufexamac
• Bupropion
• Carbamazepine
• Caspofungin
• Celecoxib
• Ceritinib
• Cerivastatin
• Cholic Acid
• Choline Salicylate
• Clonixin
• Cobicistat
• Conivaptan
• Crizotinib
• Cyclophosphamide
• Dabigatran Etexilate
• Dasabuvir
• Deflazacort
• Dexibuprofen
• Dexketoprofen
• Diclofenac
• Diflunisal
• Diltiazem
• Diphtheria Toxoid, Adsorbed
• Dipyrone
• Domperidone
• Donepezil
• Doxorubicin
• Doxorubicin Hydrochloride Liposome
• Droxicam
• Efavirenz
• Eliglustat
• Eluxadoline
• Enzalutamide
• Etodolac
• Etofenamate
• Etoposide
• Etoricoxib
• Etravirine
• Felbinac
• Felodipine
• Fenoprofen
• Fepradinol
• Feprazone
• Floctafenine
• Fluconazole
• Flufenamic Acid
• Flurbiprofen
• Foscarnet
• Golimumab
• Guselkumab
• Haemophilus B Vaccine
• Hepatitis A Vaccine, Inactivated
• Ibuprofen
• Ibuprofen Lysine
• Idelalisib
• Indomethacin
• Infliximab
• Influenza Virus Vaccine
• Isavuconazonium Sulfate
• Itraconazole
• Ketoprofen
• Ketorolac
• Lanreotide
• Lornoxicam
• Lovastatin
• Loxoprofen
• Lumacaftor
• Lumiracoxib
• Lyme Disease Vaccine (Recombinant OspA)
• Measles Virus Vaccine, Live
• Meclofenamate
• Mefenamic Acid
• Meloxicam
• Meningococcal Vaccine
• Morniflumate
• Morphine
• Morphine Sulfate Liposome
• Mumps Virus Vaccine, Live
• Mycophenolic Acid
• Nabumetone
• Nafcillin
• Naproxen
• Nepafenac
• Netupitant
• Nicardipine
• Niflumic Acid
• Nimesulide
• Nimesulide Beta Cyclodextrin
• Octreotide
• Ombitasvir
• Oxaprozin
• Oxyphenbutazone
• Parecoxib
• Paritaprevir
• Pazopanib
• Perindopril
• Pertussis Vaccine
• Phenylbutazone
• Piketoprofen
• Piperaquine
• Piroxicam
• Pitolisant
• Pixantrone
• Plague Vaccine
• Pneumococcal Vaccine, Diphtheria Conjugate
• Pneumococcal Vaccine Polyvalent
• Poliovirus Vaccine, Live
• Posaconazole
• Pravastatin
• Proglumetacin
• Propionic Acid
• Propyphenazone
• Proquazone
• Pyrazinamide
• Rabies Vaccine
• Ranolazine
• Red Yeast Rice
• Ribociclib
• Rifabutin
• Rifampin
• Ritonavir
• Rofecoxib
• Rosuvastatin
• Rotavirus Vaccine, Live
• Rubella Virus Vaccine, Live
• Salicylic Acid
• Salsalate
• Secukinumab
• Silodosin
• Simeprevir
• Smallpox Vaccine
• Sodium Salicylate
• St John's Wort
• Sulfinpyrazone
• Sulindac
• Tacrolimus
• Telaprevir
• Telithromycin
• Tenoxicam
• Tetanus Toxoid
• Tiaprofenic Acid
• Tolfenamic Acid
• Tolmetin
• Topotecan
• Typhoid Vaccine, Live
• Valdecoxib
• Varicella Virus Vaccine
• Venetoclax
• Vilazodone
• Vincristine
• Vincristine Sulfate Liposome
• Voriconazole
• Yellow Fever Vaccine

Using this medicine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Acetazolamide
• Allopurinol
• Ambrisentan
• Amiodarone
• Amphotericin B
• Amphotericin B Cholesteryl Sulfate Complex
• Amphotericin B Lipid Complex
• Amphotericin B Liposome
• Amprenavir
• Boceprevir
• Bromocriptine
• Chloramphenicol
• Chloroquine
• Cimetidine
• Ciprofloxacin
• Cisapride
• Clarithromycin
• Clonidine
• Colesevelam
• Dalfopristin
• Danazol
• Desogestrel
• Dienogest
• Digoxin
• Dirithromycin
• Drospirenone
• Erythromycin
• Estradiol Cypionate
• Estradiol Valerate
• Ethinyl Estradiol
• Ethynodiol Diacetate
• Etonogestrel
• Ezetimibe
• Famotidine
• Fenofibrate
• Fluvoxamine
• Fosamprenavir
• Fosphenytoin
• Furosemide
• Glipizide
• Glyburide
• Imipenem
• Indinavir
• Josamycin
• Ketoconazole
• Levonorgestrel
• Medroxyprogesterone Acetate
• Mestranol
• Methotrexate
• Methylprednisolone
• Metoclopramide
• Metronidazole
• Mibefradil
• Midazolam
• Miokamycin
• Modafinil
• Mycophenolate Mofetil
• Nefazodone
• Nelfinavir
• Nevirapine
• Norelgestromin
• Norethindrone
• Norfloxacin
• Norgestimate
• Norgestrel
• Oxypurinol
• Phenytoin
• Probucol
• Propafenone
• Quinine
• Quinupristin
• Repaglinide
• Rifapentine
• Saquinavir
• Sulfadiazine
• Sulfasalazine
• Terbinafine
• Tobramycin
• Tolterodine
• Troglitazone
• Verapamil
• Warfarin

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Allergy to polyoxyethylated castor oil (Cremophor® EL)—Should not be used in patients with this condition.

• Anemia or
• Bleeding problems or
• Brain disease (e.g., encephalopathy) or
• Cancer or
• Eye or visual problems (e.g., papilloedema) or
• Hyperkalemia (high potassium in the blood) or
• Hypertension (high blood pressure) or
• Hyperuricemia (too much uric acid in the blood) or
• Kidney disease or
• Liver disease or
• Precancerous skin changes or
• Seizures, history of or
• Thrombocytopenia (low number of platelets)—Use with caution. May make these conditions worse. .

• Hypertension (high blood pressure) or
• Hypocholesterolemia (low cholesterol in the blood) or
• Hypomagnesemia (low magnesium in the blood)—May increase risk for encephalopathy.

• Infection—May decrease body's ability to fight infection.

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

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

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

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

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

Common side effects of Sandimmune include: hirsutism, hypertension, increased blood urea nitrogen, increased serum creatinine, nephrotoxicity, and tremor. See below for a comprehensive list of adverse effects.

Applies to cyclosporine: oral capsule, oral capsule liquid filled, oral solution

Other dosage forms:

• intravenous solution

Along with its needed effects, cyclosporine (the active ingredient contained in Sandimmune) may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking cyclosporine:

• Abdominal or stomach pain or tenderness
• back pain
• black, tarry stools
• blurred vision
• chest pain
• chills
• clay colored stools
• cloudy urine
• cough
• dark urine
• decrease in urine output or decrease in urine-concentrating ability
• decreased appetite
• dizziness
• drowsiness
• fever
• headache
• headache, severe and throbbing
• itching
• loss of appetite
• muscle spasms (tetany) or twitching
• nausea and vomiting
• nervousness
• painful or difficult urination
• pounding in the ears
• shakiness in the legs, arms, hands, or feet
• shortness of breath
• skin rash
• slow or fast heartbeat
• sore throat
• sores, ulcers, or white spots on the lips or in the mouth
• swelling of the feet or lower legs
• swollen glands
• trembling or shaking of the hands or feet
• unusual bleeding or bruising
• unusual tiredness or weakness
• yellow eyes or skin

• Bleeding gums
• blood in the urine
• blood in the vomit
• burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings
• convulsions
• difficulty swallowing
• hives
• pale skin
• pinpoint red spots on the skin
• puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
• severe or continuing stomach pain
• tightness in the chest
• troubled breathing with exertion

• Bloating
• chest discomfort
• constipation
• darkened urine
• hoarseness
• indigestion
• lower back or side pain
• night sweats
• pain or discomfort in the arms, jaw, back, or neck
• pains in the stomach, side, or abdomen, possibly radiating to the back
• sweating
• vomiting of blood or material that looks like coffee grounds

Some side effects of cyclosporine may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Abdominal or stomach discomfort
• bleeding, tender, or enlarged gums
• blemishes on the skin
• increased hair growth, especially on the face
• pain or tenderness around the eyes and cheekbones
• pimples
• stuffy or runny nose

• Brittle fingernails
• burning feeling in the chest or stomach
• burning, dry, or itching eyes
• continuing ringing or buzzing or other unexplained noise in the ears
• cramps
• discharge or excessive tearing
• feeling of warmth
• hearing loss
• redness of the face, neck, arms, and occasionally, upper chest
• redness, pain, swelling of the eye, eyelid, or inner lining of the eyelid
• swelling of the breasts or breast soreness in both females and males
• weight loss

• Blurred or loss of vision
• discouragement
• disturbed color perception
• double vision
• fear
• feeling sad or empty
• halos around lights
• irritability
• joint pain
• loss of interest or pleasure
• night blindness
• overbright appearance of lights
• tiredness
• trouble concentrating
• trouble sleeping
• tunnel vision
• unusual drowsiness, dullness, tiredness, weakness, or feeling of sluggishness
• weakness
• weight loss