Immunosuppressant drugs include-

Azathioprine, Tacrolimus (FK 506 ), Mycophenolate Mofetil, Cyclosporine, Muromonab -CD3, 

Interacting drugs- summary

+Tacrolimus -

Nephrotoxic agents/  Aminoglycosides / Amphotericin B  / Cisplatin / Cyclosporine 
 potential for additive  or synergistic impairment of renal function
 Take care while administering tacrolimus with these drugs

Antifungals /  Bromocriptine /  Cal chnl blockrs/Cimetidine /Clarithromycin /Danazol /  Diltiazem / Erythromycin  /Methyl prednisolon / Metoclopramide
 these agents may increase tacrolimus blood levels      
       
 Carbamazepine  /  Phenobarbital/   Phenytoin / Rifamycins
   these agents may decrease tacrolimus blood levels

Itraconazole  
coadmin has lead to increased tracrolimus plasma concentrations

Tacrolimus +
Vaccines  
 immunosuppressants may affect vaccination.  
            

ASTAGRAF XL. (tacrolimus extended-release capsules), for oral use                    Initial U.S. Approval: 2013

Approved by FDA on April 8, 1994

Immunosuppressant drugs include-
Azathioprine, Tacrolimus (FK 506 ), Mycophenolate Mofetil, Cyclosporine, Muromonab -CD3,

 Organ(liver) prophylaxis

INFORMATION UPDATE-

TOPICAL TACROLIMUS- USE AS LAST RESORT

Topical tacrolimus should not be used-

To treat atopic eczema

Even when atopic eczema is moderate to severe , tacrolimus should not be used as a
-first line of treatment . It should not be used before other treatements  are tried

Tacrolimus may be considered to treat moderate or severe atopic eczema if the maximum
strength and potency of topical coticosteroids has been tried and has not worked, or where
there is a serious risk of important side effects from further use of topical corticisteroids.

European Medicines Evaluation Agency ( EMEA ) has recommended greater caution in order
to reduce potential risks of skin cancer and lymphoma. ( MIMS )  

Principal adverse reactions are- tremor, headache, diarrhea, hypertension, nausea, and renal
dysfunction.

Others incude -
Abnormal dreams, agitation, anxiety, confusion, convulsion, depression, dizziness, emotional
stability, hallucinations, hypertonia, incordination, myoclonus nervousness, neuropathy,
psychosis, somnolence, thinking abnormal. 

Special senses- abnormal vision, amblyopia, tinnitus

GI- Chlangitis, cholestatic jaundice, dyspepsia, dysphasia, flatulence, GI hemorrhage,  GI peforation,hepatitis, ileus, increased appetite, jaundice, liver damage, oral moniliasis.

Cardiovascular- chest apin, abnormal ECG, hemorrhage, hypotension, tachycardia,

GU- hematuria, kidney failure

Metabolic/Nutrional- acidosis, alkaline phosphatase,increased alkalosis, bilirubinenima,
hypophosphatemia, hyponatreamia, AST increased, ALT decreased

Miscellaneous- arthalgia, generalized spasm., leg cramps, myalgia, myastenia, osteoporosis

Respiratory- asthma, bronchitis, cough increased, lung disorder, pulmonary edema, pharyngitis,
 pneumonia, respiratory disorder, rhinitis, sinusitis, voice alteration

Dermatologic- alopecia, herpes simplex, hirsutism, skin disorder, sweating

Hypersens to the drug

Special precautions:
Monitor regularly serum creatinine and potassium. Hyperetension is a common adverse effect
Hyperglycemia

Monitoring- Regularly assess serum creatinine and potassium. Perform routine monitoring of
 metabolic  and hematolgic systems as clinically warranted

Hypertension- is common adverse efect of tracolimus therap . Mild or moderate hypertension is more
 frequently reported than severe hypertension. antihypertensive therapy may be required

Hyperglycemia- was associated with use of tracolimus in 29% to 47% of liver plant receipients and
may require treatment

Warnings-
Nephrotoxicity- tacrolimus can cause nephrotoxicity, particularly when used in high doses, particularly
 when used in high doses.

Hyperkalemia- Mild to severe hyperkalemia has been noted in 10% to 44% of liver transplant
receipents treated  with tacrolimus,which may require treatment. Monitor serum paotassium levels and
 do not use potassium spaing diuretics therapy

Neurotoxicty- neurotoxicity including tremor, headache and otherchanges inmotor function status and
sensory function occured in about 55% of liver transplant recipients. Com and delirium also have been
 associated withhigh plasma concentrations of tracolimus.

Lymphomas- because of the danger of oversuppression of the immune system,which can increase
susceptibility to infection, do not adminster tracolimus with other immunosuppressive agents except
adrenal corticosteroids.
The efficacy and safety of the use of tacromilus in combination with other immunosuppressive agents
 has not been determined  

Hypersentivity- a few patients receiving the injection have experienced anphylactic reactions.
Although the exact cause of these raections is not known , other drugs with castor oil derivatives have
 been associated with anaphylaxis in small percentage of patients

Renal/function function impairment- use lower doses for patients for patients with renal insufficiency.
 Use of tracolimus in liver transparent receipients experiencing post-transplant  hepatic impairment
 may be associated with increased risk of developing renal insufficiency related to high whole-blood
 levels of tracolimus.
Monitor these patients closely and consider dosage adjustments. Use lower doses in these patients

Carcinogenesis/Fertility impairment- it has been reported that reduction or discontiuation of
 immunosuppression may cause the lesions to regress.

Pregnancy- the use of tracolimus during pregnancy has associated with neonatal hyperkalemia
and renal dysfunction

Lactaction- since tacrolimus is excreted in breast milk, avoid nusring.

Children- pediatric patients generally require higher doses to maintain blood trough levels of
 tacrolimus similar to adult patients

Approved by FDA on April 8, 1994

Organ(liver) prophylaxis

Dosage:

Injection:

For IV infusion only

Overdosage- There is minimal experience with overdosage. In patients who have received inadvertant overdosage of tacrolimus, no adverse reactions different from those reported in patients receiving therapeutic doses have been described.

1. Follow general supportive treatment

2. Based on the poor aqueous solubility and extensive erythrocyte and plasm protein binding , it is anticipated that tacrolimus is not dialyzable to any significant extent.

Missed dose-

1. If you miss a dose of this medicine, take it as soon as possible.

2. However, if it is almost time for next dose, skip the missed dose and go back to your regular dosing schedule.

3. Do not double doses.

Pharmacology:

Tacrolimus ,previously known as FK 506., is a macrolide immunosuppressant produced by Sreptomyces tsukubaensis.

Tacromilus prolongs the survival of the host and transplanted graft in animal transplant models of liver, kidney,heart, bone marrow, small bowel and pancreas, lung and trachea, skin, cornea and limb.

Pharmacokinetics:

Absorption from GI tract after oral admin is variable. The absorption half-life in 16 liver transplant patients averaged 5.7hrs. Peak serum concentration is acheived in about 1.5 to 3.5hrs.