Pronunciation:

nye-TIS-i-none

Brand Names:

• Nityr
• Orfadin

Dosage Forms:

• Capsule
• Tablet
• Suspension

Classifications:

Therapeutic—

Gastrointestinal Agent

Uses of This Medicine:

Nitisinone is used to treat hereditary tyrosinemia type 1, which is too much tyrosine in the blood. It helps to prevent high levels of tyrosine in the blood. Treatment with nitisinone and diet changes may slow the progression of the disease, but will not cure it.

This medicine is available only with your doctor's prescription.

Before Using This Medicine:

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies—

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Children—

Appropriate studies performed to date have not demonstrated pediatric-specific problems that would limit the usefulness of nitisinone in children. Safety and efficacy have been established.

Older adults—

No information is available on the relationship of age to the effects of nitisinone capsules or oral liquid in geriatric patients. However, elderly patients are more likely to have age-related liver, kidney, or heart problems, which may require caution and an adjustment in the dose for patients receiving nitisinone capsules or oral liquid.

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of nitisinone tablets in the elderly. However, elderly patients are more likely to have age-related liver, kidney, or heart problems, which may require caution in the dose for patients receiving nitisinone tablets.

Breast-feeding—

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Other medicines—

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Deuruxolitinib

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Acyclovir
• Adefovir
• Azathioprine
• Baricitinib
• Celecoxib
• Ciprofloxacin
• Erdafitinib
• Fosphenytoin
• Furosemide
• Levoketoconazole
• Mercaptopurine
• Methadone
• Methotrexate
• Phenobarbital
• Phenytoin
• Primidone
• Seladelpar
• Sulbactam
• Sulopenem
• Tolbutamide
• Vadadustat
• Valacyclovir
• Warfarin

Other interactions—

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other medical problems—

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Conjunctivitis (eye inflammation) or
• Eye pain or
• Leukopenia (low white blood cells) or
• Photophobia (eye sensitivity to light) or
• Thrombocytopenia (low platelets in the blood)—Use with caution. May make these conditions worse.

Proper Use of This Medicine:

Take this medicine exactly as directed by your doctor. Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered. To do so may increase the chance of side effects.

Carefully follow your doctor's instructions about a special diet.

This medicine should come with a Medication Guide or patient instructions. Read and follow these instructions carefully. Ask your doctor if you have any questions.

You may take the oral liquid and tablet with or without food.

To use the capsule:

• Take the capsule on an empty stomach at least 1 hour before or 2 hours after a meal.
• If needed, you may open the capsule and put the contents in a small amount of water, formula, or applesauce. Give the medicine as soon as it is mixed.

To use the oral liquid:

• Allow the bottle to warm to room temperature for 30 to 60 minutes.
• Shake the bottle for at least 20 seconds until the solid cake at the bottom of the bottle is completely dissolved.
• Insert the bottle adapter and measure the medicine with an oral syringe.
• Shake the bottle for at least 5 seconds before measuring each dose to remove any particles at the bottom of the bottle.

To use the tablet:

• If you are unable to swallow the tablet whole, you can mix the tablet with water in an oral syringe or crush the tablet and mix with applesauce. Do not mix it with any other food or liquid.
  • To prepare for an applesauce mixture:
    • Wash your hands well before preparing the medicine.
    • Measure about 1 teaspoon of applesauce and put it into a clean container (eg, glass or bowl).
    • Place the tablet onto a spoon. Crush one tablet at a time between 2 spoons until the tablet is crushed to a fine powder.
    • Carefully place the powder into the clean container of applesauce. Make sure that no tablet powder remains on the teaspoon. If more than 1 tablet is needed, repeat the previous steps. Stir the mixture well.
    • Swallow all of the mixture right away or within 2 hours of mixing. Repeat this step until no mixture is left in the container.
    • Measure another 1 teaspoon of applesauce and place it in the container. Stir the fresh applesauce with any remaining tablet powder until mixed well. Swallow this mixture right away. This will make sure any remaining medicine in the container is administered.
  • To prepare for an oral syringe:
    • Wash your hands well before preparing the medicine.
    • Use only 1 or 2 tablets in an oral syringe at a time.
    • For 1 tablet: place the tablet in the oral syringe. Add 2.6 milliliters (mL) of room temperature water and pull the plunger back to the 3 mL mark. For 2 tablets: place the 2 tablets in the oral syringe. Add 5 mL of room temperature water.
    • Replace the cap on the syringe and let it sit for at least 15 minutes for 2 milligrams (mg) tablets and at least 60 minutes for 5 mg or 10 mg tablets.
    • Turn the syringe up and down for at least 30 seconds.
    • Check the mixture in the syringe. The tablet should have broken down into small pieces and are evenly spread in the water (suspension). Do not take the suspension if there are any large pieces of tablet in it or if there are any tablet pieces that are not evenly spread through the water.
    • If the tablet is not fully dissolved, let it sit for another 10 minutes. Then, turn the syringe up and down for at least 30 seconds.
    • Place the tip of the syringe in the mouth. If you are giving it to a child, place the tip of the syringe along the inner cheek of the child's mouth.
    • Slowly push the plunger down until a small amount of air is left in the syringe, between the plunger and the tip. Do not press the plunger all the way down to the end of the syringe.
    • Draw up an additional 2 mL of water into the syringe. Replace the cap on the syringe. Shake well to spread the remaining tablet pieces evenly through the water. If particles are still present, repeat this step one more time.

Dosing—

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For hereditary tyrosinemia type 1:
  • For oral dosage forms (capsules or suspension):
    • Adults—Dose is based on body weight and must be determined by your doctor. The starting dose is usually 0.5 milligram (mg) per kilogram (kg) of body weight 2 times a day. Your doctor may adjust the dose as needed. However, the dose is usually not more than 1 or 2 mg per kg of body weight per day.
    • Children—Dose is based on body weight and must be determined by your doctor. The starting dose is usually 0.5 mg per kg of body weight 2 times a day. Your doctor may adjust the dose as needed. However, the dose is usually not more than 1 or 2 mg per kg of body weight per day.
  • For oral dosage form (tablets):
    • Adults and children—Dose is based on body weight and must be determined by your doctor. The starting dose is usually 0.5 milligrams per kilogram (mg/kg) of body weight 2 times a day. Your doctor may adjust the dose as needed. However, the dose is usually not more than 1 to 2 mg/kg of body weight 2 times a day.

Missed dose—

If you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage—

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Store in the refrigerator. Do not freeze.

Once opened, you may store the bottle of oral liquid at room temperature for up to 60 days. Throw away any unused medicine after 60 days.

Store the tablets in its original container at room temperature. Keep the tablets and the medicine prepared in an oral syringe and with the applesauce away from direct light. Throw away unused mixture within 2 hours after mixing with applesauce or within 24 hours after mixing in the oral syringe.

Precautions While Using This Medicine:

It is very important that your doctor check your or your child's progress at regular visits to make sure this medicine is working properly. Blood and urine tests may be needed to check for unwanted effects.

Check with your doctor right away if blurred vision, difficulty seeing at night, sensitivity of the eyes to sunlight, or any other changes in vision occur during or after treatment. Your doctor may want your eyes be checked by an ophthalmologist (eye doctor).

This medicine may also cause intellectual disability and developmental delay. Check with your doctor if you or your child has problems in short-term memory, learning ability, or attention.

This medicine may cause painful hyperkeratotic plaques (skin condition) on the soles and palms. Check with your doctor right away if your skin becomes thicker than normal.

Nitisinone can temporarily lower the number of white blood cells in your blood, increasing the chance of getting an infection. It can also lower the number of platelets, which are necessary for proper blood clotting. If this occurs, there are certain precautions you can take, especially when your blood count is low, to reduce the risk of infection or bleeding:

• If you can, avoid people with infections. Check with your doctor immediately if you think you are getting an infection or if you get a fever or chills, cough or hoarseness, lower back or side pain, or painful or difficult urination.
• Check with your doctor immediately if you notice any unusual bleeding or bruising, black, tarry stools, blood in the urine or stools, or pinpoint red spots on your skin.
• Be careful when using a regular toothbrush, dental floss, or toothpick. Your medical doctor, dentist, or nurse may recommend other ways to clean your teeth and gums. Check with your medical doctor before having any dental work done.
• Do not touch your eyes or the inside of your nose unless you have just washed your hands and have not touched anything else in the meantime.
• Be careful not to cut yourself when you are using sharp objects such as a safety razor or fingernail or toenail cutters.
• Avoid contact sports or other situations where bruising or injury could occur.

The oral suspension contains glycerol and may cause diarrhea, an upset stomach, or headaches. Let your doctor know if you have these symptoms.

Side Effects of This Medicine:

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

Less common

Black, tarry stools

bleeding gums

blindness

blood in the urine or stools

bloody nose

blurred vision

burning, dry, or itching eyes

change in color vision

chest pain or discomfort

chills

cough

decreased vision

difficulty seeing at night

excessive eye tearing

eye redness, irritation, or pain

fever

increased sensitivity of the eyes to sunlight

painful or difficult urination

pinpoint red spots on the skin

redness, pain, swelling of the eye, eyelid, or inner lining of the eyelid

sore throat

sores, ulcers, or white spots on the lips or in the mouth

swollen or painful glands

thickened patches on the skin

unusual bleeding or bruising

unusual tiredness or weakness

Rare

Agitation

back pain

bluish color of the fingernails, lips, skin, palms, or nail beds

chest tightness

confusion

cough with mucus

difficulty with breathing

dizziness

drowsiness

fast heartbeat

headache

irritability

seeing or hearing things that are not there

seizures

stiff neck

vomiting

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

Less common

Dry skin

hair loss or thinning

itching or skin rash

red, swollen skin

scaly skin

Rare

Cold sweats

cool, pale skin

depression

headache

increased hunger

nausea

nightmares

shakiness

slurred speech

stomach pain

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.