0.2 mg and 1 mg granules tacrolimus for oral suspension
What Modigraf Is And What Modigraf Used For
Modigraf contains the active substance tacrolimus. It is an immunosuppressive drug. After an organ transplant (eg liver, kidney, heart), your body tries to repel the new organ. Modigraf is used to control the immune system in your body, to accept the transplanted organ.
You can also be given Modigraf for an ongoing rejection reaction in your transplanted liver, kidney, heart, or another organ when another treatment you have received has not been able to control the immune system after your transplant. Modigraf is used for adults and children.
What You Need To Know Before Taking Modigraf
Do Not Take Modigraf
- If you are allergic to tacrolimus or any of the other ingredients of this medicine (listed in section 6).
- If you are allergic to sirolimus (another substance used to prevent the rejection of transplanted organs) or to any macrolide antibiotic (eg erythromycin, clarithromycin, josamycin).
Warnings And Cautions
Talk to your doctor or pharmacist before taking Modigraf
- If you have or have had liver problems
- If you have diarrhea that lasts more than a day
- If you get severe abdominal pain accompanied or not by other symptoms, such as chills, fever, nausea or vomiting
- If you have a change in heart rhythm, so-called “QT prolongation”.
Avoid taking herbal medicines, e.g. St. John’s wort ( Hypericum perforatum ) or other herbal products as this may affect the effectiveness of Modigraf and the dose you need to take. If in doubt, consult your doctor before taking any herbal medicines or products.
Your doctor may need to adjust the Modigraf dose. You should have regular contact with your doctor, who may occasionally need tests of blood, urine, heart function, and eyes, to determine the correct dose of Modigraf.
Limit exposure to sunlight and UV light (ultraviolet light) while taking Modigraf. This is because immunosuppressive drugs such as Modigraf may increase the risk of developing skin cancer. In case of sun exposure, wear suitable protective clothing and sunscreen with a high sun protection factor.
Handling Precautions:
Direct contact with any part of the body, such as skin or eyes, or inhalation of solution for injection, powder, or granules with tacrolimus should be avoided. In such contact, skin and eyes should be rinsed.
Other Medicines And Modigraf
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
Concomitant treatment with Modigraf and ciclosporin (another medicine used to counteract the rejection of transplanted organs) is not recommended.
If you need to see a doctor other than your transplant specialist, tell your doctor that you are taking tacrolimus. Your doctor may need to consult your transplant specialist if you are taking another medicine that may increase or decrease the tacrolimus concentration in your blood.
The blood concentrations of Modigraf may be affected by other medicines you are taking and blood levels of other medicines may be affected by your taking Modigraf, which means that the Modigraf dose may need to be increased, decreased, or stopped.
In some patients, tacrolimus concentrations in the blood have increased when they were taking other medicines at the same time. This can lead to serious side effects, such as problems with the kidneys and nervous system as well as disorders of the heart rhythm (see section 4).
Effects on Modigraf concentrations in the blood can occur very quickly after starting another medicine. Therefore, continuous monitoring of the concentration of Modigraf in the blood may be needed during the first few days after you start taking another medicine and at frequent intervals for the duration of treatment with the other medicine. Some other medicines may reduce the concentration of tacrolimus in the blood, which may increase the risk of transplant rejection. You should especially tell your doctor if you are taking or have recently taken any medicines such as:
- Medicines for fungal infections and antibiotics , especially so-called macrolide antibiotics used to treat infections , e.g. ketoconazole , fluconazole , itraconazole, posaconazole, voriconazole, clotrimazole, isavuconazole, miconazole , telithromycin, erythromycin, clarithromycin, josamycin, azithromycin, rifampicin, rifabutin and isoniazid .
- Letermovir, which is used to prevent diseases caused by CMV ( cytomegalovirus in humans)
- HIV protease inhibitors (eg ritonavir, nelfinavir, saquvinavir), the booster drug cobicistat and combination tablets, or non-nucleoside reverse transcriptase inhibitors against HIV (efavirenz, etravirine, nevirapine) used to treat HIV infection
- HCV – protease inhibitors (eg telaprevir, boceprevir and the combination of ombitasvir / paritaprevir / ritonavir with or without dasabuvir, elbasvir / grazoprevir and glecaprevir / pibrentasvir), used to treat hepatitis C infection
- Nilotinib and imatinib, idelalisib, ceritinib, crizotinib, apalutamide, enzalutamide or mitotane (used to treat certain cancers)
- Mycophenolic acid, which is used to suppress the immune system to prevent rejection of the transplanted organ
- Medicines for stomach ulcers and acid reflux (eg omeprazole, lansoprazole or cimetidine)
- Medicines for nausea and vomiting (eg metoclopramide)
- Cisapride or magnesium -aluminum hydroxide, used to treat heartburn
- Birth control pills , hormone treatments containing ethinyl estradiol or hormone treatments with danazol
- Medicines for high blood pressure or heart problems (eg nifedipine, nicardipine, diltiazem and verapamil)
- Antiarrhythmics ( amiodarone ) drugs used to treat arrhythmias (irregular heartbeat)
- Drugs called ‘statins’, which are used to treat high cholesterol and triglycerides
- Carbamazepine, phenytoin and phenobarbital used to treat epilepsy
- Metamizole, which is used to treat pain and fever
- The corticosteroids prednisolone and methylprednisolone , which are used to treat inflammation and suppress the immune system (eg when rejecting the transplanted organ)
- Nefazodone used to treat depression
- Herbal medicines containing St. John’s wort ( Hypericum perforatum ) or extracts of Schisandra sphenanthera
Tell your doctor if you are receiving treatment for hepatitis C. Drug treatment for hepatitis C can affect liver function and thus the tacrolimus concentration in the blood. Tacrolimus levels in the blood may decrease or increase depending on the medicines prescribed for hepatitis C. Your doctor may need to monitor your tacrolimus levels carefully and adjust your Modigraf dose after you start treatment for hepatitis C.
Tell your doctor if you are taking or need to take ibuprofen (medicines for fever, inflammation, and pain), antibiotics (trimethoprim/sulfamethoxazole, vancomycin or aminoglycoside antibiotics such as gentamicin), amphotericin B (medicines for fungal infections), or medicines for viral infections (eg .acyclovir, ganciclovir, cidofovir, foscarnet). These can aggravate kidney problems or problems in the nervous system when taken with Modigraf.
Your doctor must also know if you are taking potassium supplements or certain diuretics, which are used for heart failure, high blood pressure, and kidney disease (eg amiloride, triamterene, or spironolactone ), certain medicines used for fever, inflammation, and pain (so-called NSAIDs), such as ibuprofen ), blood thinners or oral medication to treat diabetes while you are taking Modigraf.
If you need to be vaccinated, tell your doctor in advance.
Modigraf With Food And Drink
You should generally take Modigraf on an empty stomach or at least 1 hour before or 2 to 3 hours after a meal. Grapefruit and grapefruit juice should be avoided while you are being treated with Modigraf, as it affects your blood levels.
Pregnancy And Breastfeeding
If you take Modigraf during pregnancy, it can be transmitted to your baby through the placenta. It could affect your baby’s health or negatively affect your pregnancy.
If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor for advice before using this medicine.
Modigraf passes into breast milk. Therefore, you should not breastfeed while taking Modigraf.
Driving And Using Machines
Do not drive or use any tools or machines if you feel dizzy or sleepy, or have trouble seeing clearly after taking Modigraf. These effects are more common if you also drink alcohol.
Modigraf Contains Lactose And Sodium
Modigraf contains lactose (milk sugar). If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicine. This medicine contains less than 1 mmol sodium (23 mg) per sachet, ie essentially ‘sodium-free’.
How To Take Modigraf
- Always take this medicine exactly as your doctor has told you. Ask your doctor or pharmacist if you are unsure. Modigraf should be prescribed by doctors who are trained in treating transplant patients and who have experience using drugs that control the body’s immune system (immunosuppressive drugs).
- Make sure you get the same tacrolimus medicine every time you pick up your prescription unless your transplant doctor has decided to switch you to another tacrolimus medicine.
- This medicine should be taken twice daily. If your physical appearance has changed from the normal white granules, or if the dose instructions have been changed, talk to your doctor or pharmacist as soon as possible to make sure you have received the correct medicine.
- The starting dose to prevent rejection of your transplanted organ is determined by your doctor and is calculated according to your body weight. The starting doses immediately after transplantation are normally in the range of 0.075–0.30 mg per kg body weight per day depending on the organ transplanted. In the treatment of rejection, the same dosage can be used.
- Dose one depends on your general condition and on which another immunosuppressive drug (s) you are receiving.
- Children and young people
- Children and adolescents should take doses of Modigraf calculated in the same way as adults. In general, children need higher doses per kg of body weight to achieve the same effective blood concentrations as adults.
- After you have started treatment with Modigraf, your doctor will take blood samples frequently to arrive at the correct dose and adjust the dose from time to time. The dose of Modigraf is usually reduced by your doctor once your condition has stabilized. Your doctor will tell you exactly how many sachets to take.
- You will need to take Modigraf every day for as long as you need immunosuppression to prevent rejection of your transplanted organ. You should be in regular contact with your doctor.
- Modigraf is taken orally twice daily, usually in the morning and in the evening. Take Modigraf on an empty stomach or 2 to 3 hours after a meal. Wait at least 1 hour for the next meal.
How To Mix Modigraf Sachet Before Taking It
Your doctor will tell you how many sachets you need to open and the amount of water needed to make a suspension. To measure the exact amount of water, you can use a syringe or a graduated cylinder gauge.
- Pour the prescribed amount of water (room temperature) into a glass or cup, up to a maximum of 50 ml. Place the cup with the water on a stable surface. Do not use copper or spoons made of PVC (polyvinyl chloride) when taking Modigraf as the active substance in Modigraf may stick to PVC.
- Carefully open the number of prescribed sachets e.g. using scissors where it is marked with an arrow.
- Hold the opened sachet between your thumb and forefinger over the cup with the open side of the sachet facing down.
- Gently tap the closed side of the sachet and pour the contents of each sachet into the glass or cup of water.
- Do not use any utensils or liquid to empty the sachet. If you follow these instructions, you will get the right amount of granules from the sachet. It is normal for some granules to remain, the sachet n is made that way.
- Stir or swirl gently until the granules have completely dissolved. Suspension can be drawn up into a syringe or swallowed directly by the patient. The liquid has a sweet taste.
- Rinse the glass or cup once with the same amount of water and drink it as well. The liquid should be drunk immediately after reconstitution.
Children And Young People
If You Take More Modigraf Than You Should
If you have accidentally taken too much Modigraf, contact your doctor or nearest hospital emergency department immediately.
If You Forget To Take Modigraf
Do not take a double dose to make up for a forgotten dose. If you forget to take your Modigraf dose, wait until it is time to take your next dose and then continue as before.
If You Stop Taking Modigraf
Ending treatment with Modigraf may increase the risk of rejection of your transplanted organ. Do not stop your treatment as long as your doctor does not tell you to. If you have any further questions on the use of this product, ask your doctor or pharmacist.
Possible Modigraf Side Effects
Like all medicines, this medicine can cause side effects, although not everybody gets them. Modigraf weakens the body’s defense mechanisms (immune system), which impairs the body’s ability to fight infection. When you take Modigraf you can therefore get more infection than usual.
Serious side effects have been reported, including
- Allergic and anaphylactic reactions (a very serious allergic reaction with loss of consciousness and difficulty breathing, requiring immediate medical attention).
- Benign and malignant tumors have been reported during treatment with Modigraf.
Contact a doctor immediately if you have or suspect you have any of the following serious side effects:
Serious side effects (may affect up to 1 in 10 people):
- Gastrointestinal perforation: severe abdominal pain possibly accompanied by other symptoms, such as
- Chills
- Fever
- Nausea
- Vomiting
- Insufficient function of the transplanted organ.
- Dimsyn.
Serious uncommon side effects (may affect up to 1 in 100 people):
- Hemolytic uremic syndrome, a condition with the following symptoms:
- Low or no urine production ( acute renal failure )
- Extreme fatigue
- Yellowing of the skin or eyes (jaundice) and abnormal bruising
- Bleeding and signs of infection .
Serious rare side effects (may affect up to 1 in 1,000 people):
- Thrombotic thrombocytope purpura (or TTP):
- A condition characterized by fever and bruising under the skin that may appear as red pin-sized dots, with or without unexplained extreme fatigue, confusion, yellowing of the skin or eyes (jaundice), with symptoms of acute renal failure (low or no urine production).
- Toxic epidermal necrolysis: damage and blisters on skin or mucous membranes, red swollen skin that can become detached from large parts of the body
- Blindness
Serious very rare side effects (may affect up to 1 in 10,000 people):
- Stevens-Johnson syndrome: unexplained widespread pain in the skin, swelling of the face, severe disease with blistering of the skin, mouth, eyes and genitals, hives , swollen tongue, red or purple skin rash spreading, flaky skin.
- Torsades de Pointes:
- Change in heart rate that may, but does not have to, be accompanied by symptoms such as
- Chest pain (angina)
- Weakness
- Dizziness or nausea
- Palpitations and difficulty breathing
- Change in heart rate that may, but does not have to, be accompanied by symptoms such as
Serious side effects ar – no known frequency (frequency can not be calculated from the available data):
- Opportunistic infections (caused by bacteria, fungi, viruses and protozoa ): prolonged diarrhea, fever and sore throat.
- Benign and malignant tumors have been reported after treatment due to immunosuppression.
- Cases of pure erythrocyteplasia (a very severe decrease in red blood cell count ), haemolytic anemia (decreased red blood cell count due to increased degradation, along with fatigue) and febrile neutropenia (a decrease in white blood cells fighting infection , along with fever) has been reported. It is not known exactly how often these side effects occur. You may be asymptomatic or experience symptoms such as fatigue, lethargy , abnormal pallor, shortness of breath, dizziness, headache, chest pain and cold in the hands and feet, depending on the severity of the condition.
- Cases of agranulocytosis (severe decrease in white blood cell count along with mouth ulcers, fever and infection (s)). You may be asymptomatic or experience symptoms such as sudden fever, stiffness and sore throat.
- Allergic and anaphylactic reactions with the following symptoms:
- Sudden itchy rash ( hives )
- Swelling of the hands, feet, ankles, face, lips, mouth or throat (which may cause difficulty swallowing or breathing) and you may feel that you are about to faint.
- Posterior reversible encephalopathy syndrome (PRES):
- Headache
- Confusion
- Mood swings, seizures and visual disturbances. This may be a sign of a disease called posterior reversible encephalopathy syndrome, which has been reported in some patients treated with tacrolimus.
- Optic neuropathy (visual nerve damage):
- Problems with your vision such as blurred vision
- Changes in color vision
- Difficulty seeing details or that your field of vision is limited.
The side effects listed below can also occur after you receive Modigraf and can be serious:
Very common side effects (may affect more than 1 user in 10):
- Increased blood sugar
- Diabetes mellitus
- Increased potassium in the blood
- Difficulty sleeping
- Tremors, headaches
- Increased blood pressure
- Abnormal liver function tests
- Diarrhea
- Nausea
- Kidney problems
Common side effects (may affect up to 1 in 10 people):
- Decreased number of blood cells ( platelets , red or white blood cells )
- Increased number of white blood cells
- Changes in the number of red blood cells (seen in blood samples)
- Decreased magnesium
- Phosphate
- Potassium
- Calcium or sodium in the blood
- Increased amount of fluid in the body
- Increased amount of uric acid or fats in the blood
- Decreased appetite
- Increased acidity in the blood, other changes in blood salts (seen in blood samples)
- Anxiety
- Confusion and difficulty orienting
- Depression
- Mood swings
- Nightmares
- Hallucinations
- Mental illness
- Seizures
- Disturbances of consciousness
- Ant crawling or numbness (sometimes painful) in the hands and feet
- Dizziness
- Reduced writing ability
- Disorders of the nervous system
- Increased photosensitivity
- Eye diseases
- Earrings
- Decreased blood flow in the heart vessels
- Faster heartbeat
- Bleeding
- Partial or complete blockage of blood vessels
- Decreased blood pressure
- Shortness of breath
- Changes in the lungs
- Fluid accumulation around the lungs
- Inflammation of the throat, cough, flu-like symptoms
- Inflammation or ulcers that cause abdominal pain or diarrhea, bleeding in the stomach
- Inflammation or ulcers in the mouth
- Fluid accumulation in the abdomen
- Vomiting
- Abdominal pain
- Digestive problems, constipation
- Gas problems
- Bloating
- Loose stools
- Stomach problems
- Bile duct problems
- Yellowing of the skin due to liver problems
- Damage to liver tissue and liver inflammation
- Itching
- Rash
- Hair loss
- Acne
- Increased sweating
- Pain in joints, limbs, back and feet
- Muscle twitching
- Insufficient renal function
- Decreased urine output
- Impaired or painful urination
- General weakness
- Fever
- Accumulation of fluid in the body
- Pain and discomfort
- Increase in alkaline phosphatases in the blood
- Weight gain
- Feeling of disturbed temperature perception
Uncommon side effects (may affect up to 1 in 100 people):
- Changes in blood clotting capacity, decrease in the number of all kinds of blood cells (seen in blood samples)
- Dehydration
- Decreased protein or sugar in the blood, increased phosphate in the blood
- Coma , cerebral haemorrhage, stroke , paralysis, brain disease, speech and language difficulties, memory problems
- Clouding in the lens of the eye
- Impaired hearing
- Irregular heartbeat, cardiac arrest, decreased heart rate, heart muscle disease, enlargement of the heart muscle, heavier heartbeat, abnormal ECG , abnormal heart rate and heart rate
- Blood clot in a friend in leg or arm
- Shock
- Breathing difficulties
- Respiratory disease
- Asthma
- Obstacles in the intestinal passage
- Increased blood level of enzyme et amylase
- Regurgitation of contents from the stomach to the throat, slowed emptying of the stomach
- Skin inflammation
- Burning sensation in the sun
- Joint diseases
- Inability to urinate
- Painful menstruation and abnormal menstrual bleeding
- Decreased function of several organs
- Flu-like symptoms
- Increased sensitivity to heat and cold
- Pressure over the chest
- Nervousness or abnormal feeling
- Increase of enzyme and lactate dehydrogenase in the blood
- Weight loss
Rare side effects (may affect up to 1 in 1,000 people):
- Small skin bleeds due to blood clots
- Increased muscle stiffness
- Deafness
- Accumulation of fluid around the heart
- Acute breathing difficulties
- Cyst formation in the pancreas
- Problems with blood flow in the liver
- Severe disease with blistering of the skin, mouth, eyes and genitals, increased hair growth
- Thirst, falls, feeling of pressure over the chest, decreased mobility, sores
Very rare side effects (may affect up to 1 in 10,000 people):
- Muscle weakness
- Abnormal echocardiogram ( ECG )
- Liver failure
- Painful urination with blood in the urine
- Increased amount of adipose tissue
Children and young people
Children and adolescents may experience the same side effects as adults.
How To Store Modigraf
- Keep this medicine out of the sight and reach of children.
- Do not use this medicine after the expiry date which is stated on the carton and sachet after “EXP”. The expiration date is the last day of the specified month.
- No special temperature instructions.
- After reconstitution, the oral suspension should be taken immediately.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.
Contents Of The Package And Other Information
Content Declaration
- The active substance is tacrolimus.
One Modigraf 0.2 mg sachet contains 0.2 mg tacrolimus (as monohydrate).
One Modigraf 1 mg sachet contains 1 mg tacrolimus (as monohydrate). - The other ingredients are: Lactose monohydrate , hypromellose (E464) and croscarmellose sodium (E468).
What The Medicine Looks Like And Contents Of The Pack
- Modigraf granules for oral suspension contain white granules in sachets.
- Packs of 50 sachets are provided.
Marketing Authorization Holder And Manufacturer
Marketing Authorisation Holder
Astellas Pharma Europe BV
Sylviusweg 62
2333 BE Leiden
Netherlands
Manufacturer
Astellas Ireland Co. Ltd.
Killorglin, County Kerry, V93FC86
Ireland