II. Indications

  1. Solid Organ Transplant immunosuppression (maintenance prevention of rejection)

III. Preparations

  1. Cyclosporine (Sandimmune)
  2. Tacrolimus (Prograf)
  3. Voclosporin

IV. Adverse Effects

  1. Cardiovascular adverse effects
    1. Hypertension
    2. Hyperlipidemia (Cyclosporine)
  2. Neurologic adverse effects
    1. Headaches
    2. Tremor
    3. Neuropathy
    4. Seizures
  3. Miscellaneous adverse effects
    1. Nephrotoxicity
    2. Hyperkalemia
    3. Gingival Hyperplasia (Cyclosporine)
    4. Diabetes Mellitus (Tacrolimus)

V. Drug Interactions: Agents that increase Calcineurin Inhibitor concentrations

  1. See Cytochrome P-450 3A4
  2. Antibiotics
    1. Aminoglycosides
    2. Ofloxacin (other Fluoroquinolones such as Ciprofloxacin and Levofloxacin may be used with caution)
    3. Erythromycin (and Clarithromycin to a lesser extent)
    4. Metronidazole (Flagyl)
  3. Antifungal agents
    1. Amphoteracin B
    2. Fluconazole
    3. Itraconazole
    4. Ketoconazole
  4. Cardiovascular agents
    1. Amiodarone
    2. Spironolactone (Hyperkalemia risk)
    3. Nondihydropyridine Calcium Channel Blockers (Diltiazem, Verapamil)
  5. Foods
    1. Grapefruit (and juice)
    2. Pineapple, papaya (affect Cyclosporine)
    3. Pomegantes (and juice)
  6. Misellaneous agents
    1. Ethinyl Estradiol (Oral Contraceptives)
    2. Warfarin (Coumadin)
    3. NSAIDS (Nephrotoxicity Risk)

VI. Drug Interactions: Agents that decrease Calcineurin Inhbitor concentrations

  1. See Cytochrome P-450 3A4
  2. Antibiotics
    1. Nafcillin
    2. Rifampin
  3. Seizure medications
    1. Carbamazepine (Tegretol)
    2. Phenytoin (Dilantin)
    3. Valproic Acid
  4. Supplements
    1. Echinacea (risk of transplant rejection)
    2. St. John's Wort
  5. Gastrointestinal agents
    1. Antacids
    2. Loperamide (Imodium)
  6. Miscellaneous agents
    1. Cholestyramine

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Cost: Medications

cyclosporine (on 8/17/2016 at Medicaid.Gov Survey of pharmacy drug pricing)
CYCLOSPORINE 100 MG CAPSULE Generic $7.69 each
CYCLOSPORINE 25 MG CAPSULE Generic $1.92 each
CYCLOSPORINE MODIFIED 100 MG Generic $2.37 each
CYCLOSPORINE MODIFIED 25 MG Generic $0.63 each
CYCLOSPORINE MODIFIED 50 MG Generic $1.17 each
sandimmune (on 7/12/2016 at Medicaid.Gov Survey of pharmacy drug pricing)
SANDIMMUNE 100 MG CAPSULE Generic $7.69 each
SANDIMMUNE 25 MG CAPSULE Generic $1.92 each
tacrolimus (on 8/17/2016 at Medicaid.Gov Survey of pharmacy drug pricing)
TACROLIMUS 0.03% OINTMENT Generic $5.51 per gram
TACROLIMUS 0.1% OINTMENT Generic $5.92 per gram
TACROLIMUS 0.5 MG CAPSULE Generic $0.36 each
TACROLIMUS 1 MG CAPSULE Generic $0.48 each
TACROLIMUS 5 MG CAPSULE Generic $4.67 each
prograf (on 6/28/2016 at Medicaid.Gov Survey of pharmacy drug pricing)
PROGRAF 0.5 MG CAPSULE Generic $0.36 each
PROGRAF 1 MG CAPSULE Generic $0.48 each

Ontology: Cyclosporine (C0010592)

Definition (CHV) A drug used to help reduce the risk of rejection of organ and bone marrow transplants by the body
Definition (CHV) A drug used to help reduce the risk of rejection of organ and bone marrow transplants by the body
Definition (CHV) A drug used to help reduce the risk of rejection of organ and bone marrow transplants by the body
Definition (CHV) A drug used to help reduce the risk of rejection of organ and bone marrow transplants by the body
Definition (CHV) A drug used to help reduce the risk of rejection of organ and bone marrow transplants by the body
Definition (CHV) A drug used to help reduce the risk of rejection of organ and bone marrow transplants by the body
Definition (NCI) A natural cyclic polypeptide immunosuppressant isolated from the fungus Beauveria nivea. The exact mechanism of action of cyclosporine is not known but may involve binding to the cellular protein cytophilin, resulting in inhibition of the enzyme calcineurin. This agent appears to specifically and reversibly inhibit immunocompetent lymphocytes in the G0-or G1-phase of the cell cycle. T-lymphocytes are preferentially inhibited with T-helper cells as the primary target. Cyclosporine also inhibits lymphokine production and release. (NCI04)
Definition (NCI_NCI-GLOSS) A drug used to help reduce the risk of rejection of organ and bone marrow transplants by the body. It is also used in clinical trials to make cancer cells more sensitive to anticancer drugs.
Definition (MSH) 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).
Definition (CSP) 11-residue cyclic peptide produced by certain fungi which has antifungal and T cell specific immunosuppressive properties.
Definition (PDQ) A natural cyclic polypeptide immunosuppressant isolated from the fungus Beauveria nivea. The exact mechanism of action of cyclosporine is not known but may involve binding to the cellular protein cytophilin, resulting in inhibition of the enzyme calcineurin. This agent appears to specifically and reversibly inhibit immunocompetent lymphocytes in the G0-or G1-phase of the cell cycle. T-lymphocytes are preferentially inhibited with T-helper cells as the primary target. Cyclosporine also inhibits lymphokine production and release. Check for "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=39201&idtype=1" active clinical trials or "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=39201&idtype=1&closed=1" closed clinical trials using this agent. ("http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C406" NCI Thesaurus)
Concepts Pharmacologic Substance (T121) , Amino Acid, Peptide, or Protein (T116)
MSH D016572
SnomedCT 387467008, 255649004, 80906007
LNC LP16098-3, MTHU005140, LA16776-9
English Cyclosporin, Cyclosporin A, Cyclosporine, Cyclosporine A, Ciclosporin, cyclosporine, cyclosporine (medication), cyclosporin-A (medication), cyclosporin-A, Cyclosporin - chemical, CYCLOSPORINE, Cyclosporine [Chemical/Ingredient], cyclosporin a, cyclosporine a, ciclosporins, cycloSPORINE, ciclosporin, Cyclosporin - chemical (substance), Ciclosporin - chemical, CYA - Cyclosporin, Cyclosporin product, CSA - Cyclosporin A, CYA - Cyclosporin A, Cyclosporine (product), Cyclosporine (substance), cyclosporin, cyclosporin A, CYSP, Ciclosporin product, CsA, CycloSPORINE A, CycloSPORINE
Swedish Ciklosporin
Czech cyklosporin, Consupren, cyklosporin A
Finnish Siklosporiini
French Ciclosporine, Cyclosporine, Ciclosporine A, Cyclosporine A
Russian TSIKLOSPORIN A, TSIKLOSPORIN, ЦИКЛОСПОРИН A, ЦИКЛОСПОРИН
Japanese サイクロスポリン, シクロスポリンA, サイクロスポリンA, シクロスポリン, サンディミュン, ネオーラル, ネオメルク, アマドラ, シクポラール, パピロック
Croatian CIKLOSPORIN
Polish Cyklosporyna A
Spanish ciclosporina - sustancia química, ciclosporina - sustancia química (sustancia), ciclosporina (producto), ciclosporina (sustancia), ciclosporina A, ciclosporina, Ciclosporina, Ciclosporina A
German Cyclosporin A, Cyclosporin
Italian Ciclosporina
Portuguese Ciclosporina A, Ciclosporina

Ontology: Tacrolimus (C0085149)

Definition (NCI_NCI-GLOSS) A drug used to help reduce the risk of rejection by the body of organ and bone marrow transplants.
Definition (NCI) A macrolide isolated from Streptomyces tsukubaensis. Tacrolimus binds to the FKBP-12 protein and forms a complex with calcium-dependent proteins, thereby inhibiting calcineurin phosphatase activity and resulting in decreased cytokine production. This agent exhibits potent immunosuppressive activity in vivo and prevents the activation of T-lymphocytes in response to antigenic or mitogenic stimulation. Tacrolimus possesses similar immunosuppressive properties to cyclosporine, but is more potent.
Definition (MSH) A macrolide isolated from the culture broth of a strain of Streptomyces tsukubaensis that has strong immunosuppressive activity in vivo and prevents the activation of T-lymphocytes in response to antigenic or mitogenic stimulation in vitro.
Definition (PDQ) A macrolide isolated from the fungus Streptomyces tsukubaensis. Tacrolimus binds to the FKBP-12 protein and forms a complex with calcium-dependent proteins, thereby inhibiting calcineurin phosphatase activity and resulting in decreased cytokine production. This agent exhibits potent immunosuppressive activity in vivo and prevents the activation of T-lymphocytes in response to antigenic or mitogenic stimulation. Tacrolimus possesses similar immunosuppressive properties to cyclosporine, but is more potent. Check for "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=42009&idtype=1" active clinical trials or "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=42009&idtype=1&closed=1" closed clinical trials using this agent. ("http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C1311" NCI Thesaurus)
Concepts Organic Chemical (T109)
MSH D016559
SnomedCT 395305001, 109129008, 386975001
LNC LP15182-6, MTHU001849
English 15,19-Epoxy-3H-pyrido(2,1-c)(1,4)oxaazacyclotricosine-1,7,20,21(4H,23H)-tetrone, 5,6,8,11,12,13,14,15,16,17,18,19,24,25,26,26a-hexadecahydro-5,19-dihydroxy-3-(2-(4-hydroxy-3-methoxycyclohexyl)-1-methylethenyl)-14,16-dimethoxy-4,10,12,18-tetramethyl-8-(2-propenyl)-, monohydrate, (3S-(3R*(E(1S*,3S*,4S*)),4S*,5R*,8S*,9E,12R*,14R*,15S*,16R*,18S*,19S*,26aR*))-, Tacrolimus, Hexadecahydro-5,19-dihydroxy-3-[2-(4-hydroxy-3-methoxycyclohexyl)-1-methylethenyl]-14,16-dimethoxy-4,10,12,18-tetramethyl-8-(2-propenyl)-15,19-epoxy-3H-pyrido[2,1-c][1,4]oxaazacyclotricosine-1,7,20,21(4H,23H)-tetrone, Fujimycin, TACROLIMUS, 15,19-Epoxy-3H-pyrido(2,1-c)(1,4)oxaazacyclotricosine-1,7,20,21(4H,23H)-tetrone, 5,6,8,11,12,13,14,15,16,17,18,19,24,25,26,26a-hexadecahydro-5,19-dihydroxy-3-(2-(4-hydroxy-3-methoxycyclohexyl)-1-methylethenyl)-14,16-dimethoxy-4,10,12,18-tetramethyl-8-(2-p, Tacrolimus [Chemical/Ingredient], tacrolimus, Tacrolimus [skin], Tacrolimus [skin] (product), tacrolimus (medication), immunosuppressives tacrolimus, Tacrolimus (product), Tacrolimus (substance)
Swedish Takrolimus
Czech takrolimus, FK-506
Finnish Takrolimuusi
German Tacrolimus
Russian TAKROLIMUS, FK-506, ТАКРОЛИМУС
Japanese プログラフ, タリムス, タクロリムス水和物, タクロリムス, プロトピック, アドバグラフ, グラセプター
Spanish tacrolimús, tacrolimus, tacrolimus (producto), tacrolimús (producto), tacrolimús (sustancia), tacrolimus (piel), tacrolimus (piel) (producto), Tacrolimús, tacrolimus (sustancia), Tacrolimus
French Tacrolimus
Polish Takrolimus, FK-506
Portuguese Tacrolimus, Tacrolimo
Italian Tacrolimus

Ontology: Calcineurin inhibitor (C1562036)

Definition (MSH) Compounds that inhibit or block the PHOSPHATASE activity of CALCINEURIN.
Concepts Pharmacologic Substance (T121)
MSH D065095
SnomedCT 416587008, 416798007
English Calcineurin inhibitors, Calcineurin inhibitor, Calcineurin Antagonists, Calcineurin Inhibitors, Calcineurin Blockers, Protein Phosphatase-2B Inhibitors, Protein Phosphatase 2B Inhibitors, Protein Phosphatase 3 Inhibitors, Calcineurin antagonist, Calcineurin inhibitor (product), Calcineurin inhibitor (substance)
Spanish inhibidor de la calcineurina (producto), inhibidor de la calcineurina (sustancia), inhibidor de la calcineurina

Ontology: voclosporin (C2607219)

Concepts Amino Acid, Peptide, or Protein (T116) , Pharmacologic Substance (T121)
MSH C484071
English voclosporin