Tacrolimus (Prograf) - Uses, Dose, Side effects, Brands, MOA

Tacrolimus is a calcineurin inhibitor used as a prophylactic treatment to prevent organ rejection in transplant patients. The extended-release and immediate release formulations should not be used interchangeably, neither should the extended release formulations be used interchangeably because of the variable pharmacokinetic properties Astagrad XL and Evarsus XR in combination with other immunosuppressants are used to prevent rejection in kidney transplant patients Hecoria and Prograf in combination with other immunosuppressants are used to prevent organ rejection in kidney, heart and liver transplants recipients Tacrolimus is also used to treat Refractory rheumatoid arthritis, uveitis, Crohn's disease, myasthenia gravis, in the prevention and treatment of graft vs host disease, intestinal transplant and as maintenance therapy in patients after lung transplantation. [bg_collapse view="button-blue" color="#f7f5f5" icon="arrow" expand_text="Dose in adults" collapse_text="Dose in adults" ]

Tacrolimus Dose in Adults:

Note: The immediate-release and extended-release formulations should not be used interchangeably

Immunosuppression after solid-organ transplant:

Sublingual (off-label route): The immediate-release tablets may be administered sublingually. However, the dose may be reduced from half to one-third of the oral dose. Serum trough concentrations should be monitored for dose adjustment.


Prevention of organ rejection in transplant recipients:

  • Tacrolimus should be used in combination or as adjunctive to other immunosuppressants for the prevention of organ rejection, especially in the early post-transplant period.
  • Tacrolimus dose should be titrated based on the target trough concentrations.
  • Intravenous tacrolimus should be reserved for patients who can not tolerate oral therapy.
  • The oral dose should be administered 8 to 12 hours after the intravenous infusion is stopped.
  • Furthermore, the sublingual dose may be considered if oral therapy cannot be tolerated and the risks of anaphylaxis with intravenous administration is high.

Tacrolimus dose in Liver transplant:

Immediate release formulation:
  • 0.1 to 0.15 mg/kg/day orally in 2 divided doses, given every 12 hours (titrate to a target trough levels) in combination with corticosteroids.
  • Patients with graft dysfunction should be advised a lower dose.
Extended-release oral formulation:
  • 0.1 to 0.2 mg/kg once daily in combination with steroids
  • It should be initiated within 12 to 18 hours of the transplantation to a titrate to target trough concentrations
  • The immediate-release formulations may be converted to the extended-release formulation and vice-versa in 1:1 (mg: mg).
Intravenous dose: 0.03 to 0.05 mg/kg/day as a continuous infusion

Tacrolimus dose in Heart transplant:

  • Tacrolimus should be used in combination with an antimetabolite agent like azathioprine or mycophenolate mofetil.
  • It can also be used with mTOR kinase inhibitors like everolimus and sirolimus.
Immediate-release oral formulation: 0.075 mg/kg/day in 2 divided doses, given every 12 hours to a target trough concentrations. Intravenous dose: 0.01 mg/kg/day as a continuous infusion.

1/5th of the oral dose can be administered intravenously in cases where a switch from oral to the intravenous form is necessary.


Tacrolimus in Kidney transplant:

It should be used in combination with either azathioprine or mycophenolate mofetil. Immediate-release oral formulation:
  • 0.2 mg/kg/day in two divided doses 12 hours apart in combination with azathioprine or
  • 0.1 mg/kg/day in two divided doses in combination with mycophenolate mofetil
  • titrate the dose to a target trough concentrations.
  • If the patient is being switched from immediate-release oral formulation to the intravenous formulation, one-third (1/3rd) of the dose should be given via intravenous infusion over 24 hours.

Extended-release Tacrolimus (Advagraf, Astagraf XL):

With basiliximab induction (prior to reperfusion or within two days of transplant completion):

    • 0.15 to 0.2 mg/kg once daily (in combination with corticosteroids and mycophenolate).

Without basiliximab induction:

Preoperative dose (administer within 12 hours prior to reperfusion):

    • 0.1 mg/kg (in combination with corticosteroids and mycophenolate)

Postoperative dose (should be administered at least 4 hours after the preoperative dose and within 12 hours of reperfusion):

  • 0.2 mg/kg once daily (in combination with corticosteroids and mycophenolate).
  • The dose should be titrated to target trough concentration
  • When switching from the intravenous to the immediate-release oral formulation, initiate oral therapy 8 - 12 hours after discontinuation of the intravenous dose.
  • Switching from the immediate-release to the extended-release formulation should be based on a 1:1 (mg: mg) basis and administered once daily.

Crohn disease (perianal/ fistulizing disease) (off-label use):

Immediate-release oral formulation (limit to short-term use only because of potential toxicity)
  • Initial: 0.1 mg/kg twice daily. (titrate to the target trough levels).

Tacrolimus Dose in Graft-versus-host disease (GVHD) (off-label use):

For the Prevention of GVHD:
  • 0.03 mg/kg/day (based on lean body weight) as a continuous intravenous infusion. Treatment should begin one day (24 hours) prior to stem cell infusion and continued until the patient can tolerate medicines orally. The intravenous dose may be switched to the immediate-release medicine in a 1:4 dose and given as twice daily.
For the Treatment of GVHD:
  • Immediate-release oral formulation: 0.06 mg/kg twice daily.
  • Intravenous dose: 0.03 mg/kg/day (based on lean body weight) as continuous infusion.

Tacrolimus Dose in Lung transplant (off-label use):

Usually used in a combination regimen consisting of a corticosteroid and either azathioprine or mycophenolate. Immediate-release oral formulation:
  • 0.05 to 0.3 mg/kg/day in 2 divided doses, given every 12 hours (titrate the dose to the target trough concentrations)
  • May also be administered sublingually at half the oral dose.
  • The extended-release formulation may be used in stable patients
Intravenous infusion: 0.01 to 0.05 mg/kg as a continuous IV infusion over 24 hours

Tacrolimus Dose in Myasthenia gravis (off-label use):

Should be used in patients who remain significantly symptomatic despite on pyridostigmine: Immediate-release oral formulation:
  • 3 to 5 mg/day or 0.1 mg/kg/day, in one or two divided doses (titrate the dose to the target trough concentrations). Clinical response may take up to 6 - 12 months.

Tacrolimus Dose in Refractory Rheumatoid arthritis (off-label use):

Immediate-release oral formulation:
  • 2 to 3 mg once daily (may be used in combination with NSAID/ oral corticosteroid therapy)
  • May be used in a lower dose (1.5 mg once daily) in combination with methotrexate
  • Serum creatinine levels should be monitored during the therapy.
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Tacrolimus Dose in Children:

Tacrolimus Dose in Liver transplant:

Immediate-release oral formulation:
  • 0.15 to 0.2 mg/kg/day in 2 divided doses per day (titrate to the target trough concentrations)

Intravenous dose:

  • 0.03 to 0.05 mg/kg/day as a continuous infusion
Note: The initial postoperative dose of tacrolimus should begin 6 hours after liver and heart transplant and within 24 hours of the kidney transplant. (use of Adjunctive therapy with corticosteroids is recommended early post-transplant period). Intravenous therapy should only be used in patients who can not tolerate oral medications because of the risks of anaphylaxis. Oral therapy may be started 8 - 12 hours after the intravenous infusion has been stopped. [/bg_collapse]   [bg_collapse view="button-blue" color="#faf5f5" icon="arrow" expand_text="Renal dose" collapse_text="Renal dose" ]

Dose in Kidney disease:

Patients with renal disease may require a reduction in the dose because of the risks of tacrolimus-induced nephrotoxicity.

Hemodialysis/ peritoneal dialysis:

Supplemental doses are not required in patients on hemodialysis as it is not removed via hemodialysis or peritoneal dialysis. [/bg_collapse]   [bg_collapse view="button-blue" color="#f7f2f2" icon="arrow" expand_text="Dose in Liver disease" collapse_text="Dose in Liver disease" ]

Dose in Liver disease:

The half-life of tacrolimus is increased in patients with moderate to severe hepatic impairment (serum bilirubin >2 mg/dL or Child-Pugh score ≥10) leading to high blood levels resulting in nephrotoxicity. It can also cause liver toxicity (hepatocellular and cholestatic liver disease) Patients should be monitored closely and the dose should be adjusted based on the drug trough levels. Initiating the patient on a lower dose may be required in such situations. [/bg_collapse]   [bg_collapse view="button-blue" color="#f7f2f2" icon="arrow" expand_text="Contraindications & Warnings" collapse_text="Contraindications & Warnings" ]

Contraindications to Tacrolimus:

Allergy or sensitivity to tacrolimus, castor oils, or any other component in the formulation It should not be used in patients who have a rare genetic disorder - Netherton's syndrome.

Warnings and precautions:

      • Patients who are able to tolerate oral therapy should use it. There is a high risk of anaphylaxis from intravenous tacrolimus.
      • Anaphylaxis should be monitored in patients receiving intravenous tacrolimus. Patients should be able to take oral tablets once they are able.
      • Arrhythmias should be checked in patients, especially those who are taking antiarrhythmic drugs and amiodarone, as well as patients with electrolyte imbalances like hypokalemia and hypomagnesemia.
      • Reversible myocardial hypertrophy may also occur in patients. This can be treated with dose reductions or discontinuation.
      • Patients are at risk of developing diabetes (also known as post transplant diabetes mellitus), especially with tacrolimus use.
      • Patients who used tacrolimus experienced gastrointestinal perforation. However, most cases were due to complications of transplant surgery, infection or malignant neoplasm.
      • Tacrolimus should be administered to patients who are hyperkalemic. Avoid potassium-sparing diuretics, and any other drugs that can cause hyperkalemia.
      • Tacrolimus may cause hypertension. Avoid drugs that cause hyperkalemia. Do not use calcium channel blockers.
Infections (BOXED warning): Hospitalization or death may result from serious bacterial, viral and protozoal infections. Reactivation of latent infections like JC (John Cunningham) virus associated with progressive multifocal leukoencephalopathy, the BK virus which is associated with the polyomavirus-associated nephropathy (PVAN) and the cytomegalovirus (CMV) infection. Malignancies (Boxed warning): Tacrolimus could be associated with skin malignancies and lymphoma. Patients should apply sunscreens and limit prolonged sun exposure Nephrotoxicity: Patients who have been taking a higher dose of tacrolimus or are using concomitant drugs that can cause nephrotoxicity, such as those who have taken a longer-lasting regimen. Neurotoxicity: High doses of tacrolimus can cause tremors, headaches, delirium and seizures in patients. PRES (Posterior Reversible Encephalopathy Syndrome) is a condition that can be caused by an altered mental status, headaches, hypertension, seizures and visual disturbances. This usually improves when blood pressure stabilization is done and the drug dose reduced or discontinued. Pure red cell aplasia: Pure red cell aplasia can occur in patients who have taken mycophenolate or are at high risk for parvovirus b19 infections. Pure red cell aplasia should be diagnosed and treated immediately.

Disease-related concerns:

      • Hepatic impairment Patients with liver disease should be cautiousUse the lowest recommended dose. Use the lowest dose.
      • Renal impairmentIf post-transplant oliguria occurs, Tacrolimus should not be used. Patients with impaired kidney function should not take more than the recommended dose.

Concurrent drug therapy:

      • TheDosage of tacrolimusTo minimize the risk of nephrotoxicity, it is important to reduce Everolimus when taken with liver transplant patients.
      • Combination of Sirolimus and TacrolimusInrenal transplant patientsIt is not recommended. It can increase mortality and graft loss, increase risk of nephrotoxicity, post-transplant Diabetes Mellitus (especially after heart transplantation), impair wound heal, and cause hepatic arterial thrombosis during liver transplantation.

Concerns about dosage form of Tacrolimus:

      • US Boxed WarningThe liver transplantation of the extended-release formulation has not been approved. The extended-release formulation has been linked to increased mortality in female patients.
      • An allergic reaction to intravenous tacrolimus has been reported.
      • Lactose is found in oral tacrolimus preparations.
Other Warnings and precautions:
    • Rapid discontinuation may lead to myasthenic symptoms or myasthenic crises.
    • It is not recommended to use the immediate-release or extended-release formulations interchangeably. This could lead to graft rejection or other adverse events.
    • Tacrolimus should only be administered by a qualified physician.
    • Patients should be immunized before starting therapy. Patients should not receive live vaccines, such as the Oral Poliovirus vaccine, during therapy or within a short time after it has begun. Patients who have received live vaccines should be avoided.
    • It is important to monitor the levels of Tacrolimus.
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How to administer Tacrolimus?

Tacrolimus should be used under the supervision of an experienced physician. Intravenous tacrolimus should be given via a slow infusion over 24 hours. The solution should not be mixed with acyclovir or ganciclovir and PVC tubing should be avoided.
Oral Tacrolimus:
  • Immediate release formulation may be taken with or without food.
  • Once-daily dosing should be preferably taken in the morning and the twice-daily dose should be taken 12 hours apart.
  • In cases where the morning and the evening doses differ, the larger dose should be taken in the morning.

Combination therapy with everolimus for liver transplantation:

  • Administer tacrolimus and everolimus at the same time.

Tacrolimus granules:

  • Do not sprinkle granules on food.
  • Empty the entire contents of each packet into a glass cup. Add 15 to 30 mL of drinking water (at room temperature), mix and administer the entire contents of the cup. Administer immediately after preparation. (Note: the granules will not completely dissolve)

Extended-release formulation:

  • The extended-release tacrolimus should be taken on an empty stomach at least 1 hour prior or 2 hours after a meal. Swallow the whole capsule, do not chew, crush, or divide.
  • Take once daily in the morning at a fixed time each day.
  • If the dose is missed, it may be taken up to 14 hours (15 hours for Envarsus XR) after the scheduled time. If more than 14 hours (>15 hours for Envarsus XR) have passed, resume at the next scheduled time. (The dose should not be doubled to make up for a missed dose)
Nasogastric tube:
  • If the patient is unable to swallow the capsules, its contents may be mixed with water and flushed through a nasogastric tube. Clamp the nasogastric tube for 30 to 60 minutes after administration.
Sublingual:
  • If the patient is unable to swallow the capsules, it may be administered sublingually (at a reduced dose) by opening the immediate-release capsules and placing its contents under the tongue, allowing them to completely dissolve.

Hazardous Drugs Handling Considerations

Use appropriate precautions like wearing gloves (single) for receiving, handling, administration, and disposal. Wearing double gloves, goggles, face mask, and a protective gown is recommended if the capsules or tablets are manipulated or crushed.

Similarly, for intravenous preparation, double gloves, a protective gown, ventilated engineering controls, and closed system transfer devices (CSTDs) are recommended. [/bg_collapse]   [bg_collapse view="button-blue" color="#f7f2f2" icon="arrow" expand_text="Pregnancy & lactation" collapse_text="Pregnancy & lactation" ]

Pregnancy Risk factor C

Tacrolimus crosses the placenta and its levels may be higher in the placenta than the maternal serum. Preterm delivery, miscarriage, low birthweight, preterm birth, birth defects (including craniofacial and renal/urogenital abnormalities), renal dysfunction, transient neonatal hypokalemia, and cardiac disease have all been reported in infants of transplant recipients. As pregnancy progresses, Tacrolimus whole-blood concentrations decrease, but concentrations of unbound form rise. It may be preferable to measure unbound concentrations, particularly in females with hypoalbuminemia or anemia. Pregnant females who have had a transplant of a kidney may have a higher risk of developing infection, hypertension, or pre-eclampsia if they are using an immunosuppressant in pregnancy. Both liver transplant recipients of tacrolimus have experienced diabetes and hypertension during pregnancy.

Breast-Feeding Considerations

Breast milk contains varying amounts of Tacrolimus. It is important to consider the risks of infant exposure and the benefits to infants of breastfeeding.   [/bg_collapse]   [bg_collapse view="button-blue" color="#f7f2f2" icon="arrow" expand_text="Side effects" collapse_text="Side effects" ]

Common side effects of Tacrolimus (alphabetical order):

  • A:
    • Acne, alopecia, anemia, anorexia, anxiety, arthralgia, ascites,
  • B:
    • bile-duct abnormalities, bloating, blood disorders,
  • C:
    • cholestasis, confusion, constipation,
  • D:
    • depression, diarrhea, dizziness, dyspepsia, dyspnoea,
  • E:
  • electrolyte disturbances, edema
  • F:
    • flatulence,
  • G:
    • gastrointestinal inflammation, gastrointestinal perforation, gastrointestinal ulceration,
  • H:
    • hemorrhage, headache, hepatic dysfunction, hyperglycaemia, hyperkalaemia, hypertension, hyperuricaemia, hypokalaemia,
  • I:
    • impaired hearing, ischaemic events,
  • J:
    • jaundice,
  • L:
  • leucopenia,
  • M:
  • mood changes, muscle cramp,
  • N:
  • nausea,
  • P:
  • pancytopenia, paraesthesia, parenchymal lung disorders, peripheral neuropathy,  photophobia, pleural effusion, psychosis,
  • R:
    • renal failure, renal impairment, renal tubular necrosis,
  • S:
    • seizures, sleep disturbances, sweating,
  • T:
    • tachycardia, thrombocytopenia, thromboembolic events, tinnitus, tremor,
  • U:
    • urinary abnormalities,
  • V:
    • visual disturbances, vomiting, and
  • W:
    • weight changes.

Uncommon Side effects (alphabetical order):

Amnesia, arrhythmia, cardiac arrest, cardiomyopathy, cataract, cerebrovascular accident, coagulation disorders, coma, dermatitis, dysmenorrhoea, encephalopathy, gastrointestinal reflux disease,  heart failure, hypertonia, hypoglycemia, influenza-like symptoms, palpitation, pancreatitis, paralysis, paralytic ileus, peritonitis, photosensitivity, respiratory failure, and speech disorder.

Rare side effects:

Blindness, dehydration,  hirsutism, pericardial effusion, posterior reversible encephalopathy syndrome, respiratory distress syndrome, thrombotic thrombocytopenic purpura, toxic epidermal necrolysis, hemorrhagic cystitis, myasthenia, Stevens-Johnson syndrome, agranulocytosis, hemolytic anemia, and pure red cell aplasia. [/bg_collapse]   [bg_collapse view="button-blue" color="#f7f2f2" icon="arrow" expand_text="Monitoring parameters" collapse_text="Monitoring parameters" ] Measure three times a week the following parameters for the first few weeks and then gradually decrease the frequency:
  • Renal function,
  • Liver function,
  • serum electrolytes like magnesium, phosphorus, potassium,
  • glucose, and
  • blood pressure,
When given via the intravenous route:
  • Monitor for anaphylaxis.
  • Monitor for QT prolongation and consider echocardiographic evaluation in patients who develop features of ventricular dysfunction, renal failure, and electrolyte abnormalities.
Monitor trough levels 30 minutes prior to the next scheduled oral dose. Whole blood should be used to monitor trough levels. The frequency of monitoring of trough levels depends on the type of transplant and clinical situation.

Reference Ranges for Tacrolimus levels in the blood.

Heart transplant:

Typical whole blood trough concentrations (goals levels may vary and have not been adequately determined):
  • Days 0 - 60: 10 to 15 ng/mL
  • Months 3 - 6: 8 to 12 ng/mL
  • More than 6 months: 5 to 10 ng/mL

Kidney transplant:

Whole blood trough concentrations: Immediate release (in combination with azathioprine):
  • Months 1 - 3: 7 to 20 ng/mL
  • Months 4 - 12: 5 to 15 ng/mL
In combination with mycophenolate mofetil/IL-2 receptor antagonist (eg, basiliximab):
  • 4 - 11 ng/mL
In combination with mTOR inhibitor (everolimus):
  • 4 - 8 ng/mL for the first 2 months after transplant followed by 3 - 5 ng/mL thereafter
Extended-release (Astagraf XL): Adult: With basiliximab induction:
  • Month 1: 7 - 15 ng/mL
  • Months 2 - 6: 5 - 15 ng/mL
  • More than 6 months: 5 - 10 ng/mL
Without basiliximab induction:
  • Month 1: 10 - 15 ng/mL
  • Months 2 - 6: 5 - 15 ng/mL
  • More than 6 months: 5 - 10 ng/mL

Reference ranges in Pediatric age groups:

With basiliximab induction:
  • Month 1: 10 - 20 ng/mL
  • More than one month: 5 - 15 ng/mL
Extended-release (Envarsus XR):
  • Month 1: 6 - 11 ng/mL
  • More than 1 month: 4 - 11 ng/mL

Liver transplant:

Whole blood trough concentrations:
  • Months 1 - 12: 5 - 20 ng/mL
When administered in combination with everolimus for liver transplant:
  • By 3 weeks after first everolimus dose and through month 12 post-transplant: 3 to 5 ng/mL

Intestinal transplant (off-label use):

  • Months 1 - 3: 10 - 20 ng/mL followed by a gradual dose reduction

Crohn disease (fistulizing disease; off-label use):

  • Whole blood concentration target range: 10 - 20 ng/mL

Lung transplant (off-label use):

  • Whole blood trough concentrations: 5 - 15 ng/mL

Myasthenia gravis (off-label use):

  • Whole blood trough concentrations: 8 - 9 ng/mL

Prevention of graft-versus-host disease (off-label use):

  • Whole blood trough concentrations: 10 - 20 ng/mL
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Mechanism of Action of Tacrolimus:

It suppresses cellular immunity by inhibiting T lymphocyte activation and Interleukin 2 production.

Pharmacodynamics and Pharmacokinetics

    • Absorption:
      • Orally, absorption can be variable due to food containing high-fat.
      • Mucositis, an inflammatory condition of the stomach, can also affect oral absorption. Patients who have had their stomas resected will absorb more.
      • Also, unlike cyclosporine clamping the T-tube in patients with liver transplants does not affect the trough levels or AUC.
    • It is distributed to the erythrocytes and kidneys, liver, spleen and heart.
    • The drug is bound to approximately 99% of proteins, mainly to albumin and alpha-1- acid glycoprotein.
    • The liver metabolizes it extensively via CYP3A4.
    • Half-life elimination
      • Children undergoing kidney transplantation take between 5 and 15 hours.
      • In infants and children with liver transplantation, it takes 7.5 to 14.5 hours
      • Variable in adults, when immediate release formulations are taken
        • Healthy volunteers spend 23 to 46 hours on average
        • Transplant patients spend between 2.1 and 36 hours.
      • Extended-release formulation: 35-41 hours (prolonged for patients with severe hepatic impairment).
    • The time it takes to reach peak plasma levels is between 0.5 and 6 hours
    • Feces are the main route of excretion
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Pricing: United States

Capsule ER 24 Hour Therapy Pack (Astagraf XL Oral)
  • 0.5 mg (per each): $2.83
  • 1 mg (per each): $5.65
  • 5 mg (per each): $28.26
Capsules (Prograf Oral)
  • 0.5 mg (per each): $3.62
  • 1 mg (per each): $7.24
  • 5 mg (per each): $36.19
Capsules (Tacrolimus Oral)
    • 0.5 mg (per each): $1.56 - $2.23
    • 1 mg (per each): $2.78 - $4.46
    • 5 mg (per each): $12.20 - $22.30
Solution (Prograf Intravenous)
    • 5 mg/mL (per mL): $249.49
Tablet, 24-hour (Envarsus XR Oral)
    • 0.75 mg (per each): $4.55
    • 1 mg (per each): $6.07
    • 4 mg (per each): $24.28

Brand Names: US

    • Astagraf XL
    • Envarsus XR
    • Prograf

Brand Names: Canada

    • Advagraf
    • Prograf

Brand Names: International

    • Adoport
    • Adport
    • Advagraf
    • Advagraf XL
    • Advahraf
    • Capexion
    • Cidimus
    • Envarsus
    • Graceptor
    • Modigraf
    • Pangraf
    • Panraf
    • Prograf
    • Prograf XL
    • Prograft
    • Prohraf
    • Regraf
    • Rolitac
    • T-Inmun
    • Taccin
    • Tacgraf
    • Tacrobell
    • Tacrocel
    • Tacrotec
    • Tacroz Forte
    • Tagraf
    • Tarimus
    • Treczimus
    • Vingraf
    • Vivadex
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Tacrolimus Brands in Pakistan:

Tacrolimus [Oint 0.1 %W/W]

Crolimus Valor Pharmaceuticals
Edtac Amarant Pharmaceuticals (Pvt)
Tacrus Shrooq Pharmaceuticals
 

Tacrolimus [Oint 0.01 %W/W]

Aimus Aims Traders
Eczemus Brookes Pharmaceutical Laboratories (Pak.) Ltd.
 

Tacrolimus [Oint 0.03 %W/W]

Aimus Aims Traders
Crolimus Valor Pharmaceuticals
Eczemus Brookes Pharmaceutical Laboratories (Pak.) Ltd.
Limus Nabiqasim Industries (Pvt) Ltd.
Limus-J Ambrosia Pharmaceuticals
Tacroderm Sante (Pvt) Limited
Tacrogen Biogen Pharma
Tacrol Acme Laboratories Pakistan (Pvt) Ltd.
Taczam Laderly Bio-Tech Pharma
 

Tacrolimus [Cream 0.1 %W/W]

Tacro Wise Pharmaceuticals (Pvt) Ltd
Tacro Wise Pharmaceuticals (Pvt) Ltd
 

Tacrolimus [Cream 0.03 %W/W]

Tagora Rogen Pharmaceuticals
 

Tacrolimus [Tabs 1 Mg]

Imunol Saffron Pharmaceutical Company
 

Tacrolimus [Caps 1 Mg]

Inograf Platinum Pharmaceuticals (Pvt.) Ltd.
Tacgraf Consolidated Chemical Laboratories (Pvt) Ltd.
Tacogen Allmed Labs
 

Tacrolimus [Caps 5 Mg]

Inograf Platinum Pharmaceuticals (Pvt.) Ltd.
 

Tacrolimus [Caps 0.5 Mg]

Inograf Platinum Pharmaceuticals (Pvt.) Ltd.
Tacgraf Consolidated Chemical Laboratories (Pvt) Ltd.
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