Consumer medicine information

1. Why am I using Tacrolimus Sandoz

Tacrolimus Sandoz contains the active ingredient tacrolimus monohydrate.
Tacrolimus Sandoz is used so that your new liver, kidney, lung or heart will not be attacked or rejected by your body.
For more information, see Section 1. Why am I using Tacrolimus Sandoz? in the full CMI.

2. What should I know before I use Tacrolimus Sandoz?

Do not use if you have ever had an allergic reaction to Tacrolimus Sandoz, macrolide antibiotics, or any of the ingredients listed at the end of the CMI. Tacrolimus Sandoz and Tacrolimus XR Sandoz are not interchangeable.
For more information, see Section 2. What should I know before I use Tacrolimus Sandoz? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with Tacrolimus Sandoz and affect how it works.
Tell your doctor of pharmacist if you are taking any other medicines, including any medicines, vitamins or supplements that you buy without a prescription from your pharmacy, supermarket or health food shop.
A list of these medicines is in Section 3. What if I am taking other medicines? in the full CMI.

4. How do I use Tacrolimus Sandoz?

• Tacrolimus Sandoz capsules should be taken in two doses (e.g. morning or evening) each day.

• Tacrolimus Sandoz capsules should be taken at least 1 hour before or 2 to 3 hours after a meal preferably with water and not grapefruit juice.

5. What should I know while using Tacrolimus Sandoz?

6. Are there any side effects?

There are a number of side effects associated with this medicine. It is important to be aware of them so that you can identify any symptoms if they occur (see the full CMI for more details). The serious side effects are: signs of allergy; fever; diabetes / increased blood sugar; swelling, numbness or tingling in your hands and feet; constant flu-like symptoms; unusual bleeding or bruising; high blood pressure; palpitations, abnormal heart rhythms, chest pain; new lumps or moles, or changes to existing moles; swelling of the eyelids, hands or feet due to excess fluid; a change in the amount of urine passed or in the number of times you urinate, pain on urinating, or other kidney problems; yellowing of the skin and/or eyes (jaundice); symptoms of anaemia; seizures (fits); buzzing or ringing in the ears, difficulty hearing.
For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.

1 Name of Medicine

Tacrolimus monohydrate.

2 Qualitative and Quantitative Composition

Tacrolimus Sandoz capsules. Each 0.5 mg capsules contains 0.5 mg tacrolimus (as monohydrate).
Each 0.75 mg capsules contains 0.75 mg tacrolimus (as monohydrate).
Each 1.0 mg capsules contains 1.0 mg tacrolimus (as monohydrate).
Each 2.0 mg capsules contains 2.0 mg tacrolimus (as monohydrate).
Each 5.0 mg capsules contains 5.0 mg tacrolimus (as monohydrate).
Excipients with known effect. Each capsule contains sugars (as lactose monohydrate).
For the full list of excipients, see Section 6.1 List of Excipients.
Tacrolimus XR Sandoz prolonged-release capsules. Each 0.5 mg prolonged-release hard capsule contains 0.5 mg tacrolimus (as monohydrate).
Each 1 mg prolonged-release hard capsule contains 1 mg tacrolimus (as monohydrate).
Each 2 mg prolonged-release hard capsule contains 2 mg tacrolimus (as monohydrate).
Each 3 mg prolonged-release hard capsule contains 3 mg tacrolimus (as monohydrate).
Each 5 mg prolonged-release hard capsule contains 5 mg tacrolimus (as monohydrate).
Excipients with known effect. Each capsule contains tartrazine (0.5 mg and 2 mg only), lactose, and sugars (as lactose monohydrate).
The printing ink used to mark the capsule contains trace amounts of soya lecithin.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Tacrolimus Sandoz capsules. Capsule. Supplied as:
Tacrolimus Sandoz 0.5 mg: White to off-white powder filled in size "4" capsule with white coloured opaque body and ivory coloured cap.
Tacrolimus Sandoz 0.75 mg: White to off-white powder filled in size "4" capsule with light green opaque body and cap, imprinted in black with 0.75 mg on cap.
Tacrolimus Sandoz 1 mg: White to off-white powder filled in size "4" capsule with white coloured opaque body and light brown coloured cap.
Tacrolimus Sandoz 2 mg: White to off-white powder filled in size "4" capsule with dark green opaque body and cap, imprinted in black with 2 mg on cap.
Tacrolimus Sandoz 5 mg: White to off-white powder filled in size "3" capsule with white coloured opaque body and Swedish orange coloured cap.
Tacrolimus XR Sandoz prolonged-release capsules. Prolonged-release capsule. Supplied as:
Tacrolimus XR Sandoz 0.5 mg prolonged-release capsules: White to yellowish powder or compacted powder filled in size "5" capsule with a light brown body and a light yellow cap, imprinted in black with "0.5 mg".
Tacrolimus XR Sandoz 1 mg prolonged-release capsules: White to yellowish powder or compacted powder filled in size "4" capsule with a light brown body and a white cap, imprinted in black with "1 mg".
Tacrolimus XR Sandoz 2 mg prolonged-release capsules: White to yellowish powder or compacted powder filled in size "3" capsule with a light brown body and a dark green cap, imprinted in black with "2 mg".
Tacrolimus XR Sandoz 3 mg prolonged-release capsules: White to yellowish powder or compacted powder filled in size 2 capsule with a light brown body and a light orange cap, imprinted in black with "3 mg".
Tacrolimus XR Sandoz 5 mg prolonged-release capsules: White to yellowish powder or compacted powder filled in size 0 capsule with a light brown body and a pink cap, imprinted in black with "5 mg".
Not all strengths may be marketed in Australia.

4 Clinical Particulars

4.9 Overdose

Symptoms. Experience of overdosage is limited. Several cases of accidental overdosage have been reported; symptoms have included tremor, headache, nausea and vomiting, infections, urticaria, lethargy, increased blood urea nitrogen and elevated serum creatinine concentrations, and increase in alanine aminotransferase levels.
Early clinical experience (when initial induction doses were two to three times greater than those currently recommended) suggested that symptoms of overdosage may include glucose intolerance, renal, neurological and cardiac disorders, hyperkalaemia and hypertension. Over immunosuppression may increase risk of severe infections.
Liver function clearly influences all pre- and postoperative pharmacokinetic variables. Patients with failing liver grafts or those switched from other immunosuppressive therapy to Tacrolimus Sandoz or Tacrolimus XR Sandoz should be monitored carefully to avoid overdosage.
Treatment. No specific antidote to tacrolimus therapy is available. If overdosage occurs, general supportive measures and symptomatic treatment should be conducted.
Based on the poor aqueous solubility and extensive erythrocyte and plasma protein binding, it is anticipated that Tacrolimus Sandoz or Tacrolimus XR Sandoz will not be dialysable. Data on haemoperfusion are not available. Activated charcoal may reduce absorption of the drug if given within one or two hours after ingestion. In patients who are not fully conscious or have impaired gag reflex, consideration should be given to administering activated charcoal via a nasogastric tube, once the airway is protected.
For information on the management of overdose, contact the Poisons Information Centre on 131126 (Australia).

5 Pharmacological Properties

5.3 Preclinical Safety Data

Genotoxicity. No evidence of genotoxicity was seen in a series of assays for gene mutations and clastogenicity. Tacrolimus did not cause unscheduled DNA synthesis in rodent hepatocytes but high concentrations of tacrolimus have been reported to increase the frequency of sister chromatid exchanges in human lymphocytes in vitro.
Carcinogenicity. Tacrolimus did not show any tumorigenic effects in long-term carcinogenicity studies using the mouse and rat. The maximum dose tested in the rat resulted in a blood exposure less than, and a plasma exposure 1.4 times, the exposure achieved after the maximum recommended clinical dose, 0.3 mg/kg, based on area under the curve (AUC). In mice the maximum dose was 0.8 times the recommended clinical dose based on body surface area.
Patients receiving long-term immunosuppressive therapy are at an increased risk of developing lymphomas and other malignancies (see Section 4.4 Special Warnings and Precautions for Use, Malignancies).

6 Pharmaceutical Particulars

6.7 Physicochemical Properties

Tacrolimus appears as white crystals or a crystalline powder, very soluble in methanol and chloroform, freely soluble in acetone and ethanol and practically insoluble in hexane and water. It is obtained by fermentation as a single enantiomer but exists in tautomeric equilibration in aqueous solution.
Chemical structure.
https://stagingapi.mims.com/au/public/v2/images/fullchemgif/CSTACMON.gif Chemical formula: [3S[3R*[E (1S*,3S*,4S*)], 4S*,5R*,8S*,9E, 12R*,14R*,15S*,16R*, 18S*,19S*,26aR*]]- 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) -15, 19-epoxy-3H-pyrido [2,1c][1,4] oxaazacyclotricosine-1,7,20, 21 (4H,23H)-tetrone, monohydrate.
Molecular formula: C₄₄H₆₉NO₁₂.H₂O.
Molecular weight: 822.03.
CAS number. 109581-93-3.

7 Medicine Schedule (Poisons Standard)

S4 - Prescription Only Medicine.

Summary Table of Changes

https://stagingapi.mims.com/au/public/v2/images/fulltablegif/TACSANST.gif