Nitisinone

Name: Nitisinone

Nitisinone Drug Class

Nitisinone is part of the drug class:

  • Various alimentary tract and metabolism products

How should I take nitisinone?

Follow all directions on your prescription label. Do not take this medicine in larger or smaller amounts or for longer than recommended.

Your doctor may occasionally change your dose to make sure you get the best results. Do not change your medication dose or schedule without your doctor's advice.

Take the nitisinone capsule on an empty stomach, at least 1 hour before or 2 hours after a meal.

You may take nitisinone liquid with or without food.

You may open the nitisinone capsule and sprinkle the medicine into a spoonful of water, baby formula, or applesauce to make swallowing easier. Use the mixture right away. Do not save for later use.

Shake the oral suspension (liquid) for at least 5 full seconds just before you measure a dose. Measure liquid medicine with the dosing syringe provided, or with a special dose-measuring spoon or medicine cup. If you do not have a dose-measuring device, ask your pharmacist for one.

Nitisinone may be only part of a complete program of treatment that also includes a special diet. You must avoid certain foods for your treatment to be effective. Follow the diet plan created for you by your doctor or nutrition counselor.

High protein foods are high in tyrosine and phenylalanine. Since babies and children need protein to grow and develop, special foods have been developed to replace the high protein foods.

While using nitisinone, you may need frequent blood tests at your doctor's office. Your vision may also need to be checked.

Store nitisinone capsules or liquid in the refrigerator, do not freeze.

After using nitisinone liquid for the first time, you may store the medicine at room temperature for up to 60 days.

What should I avoid while taking nitisinone?

While you are taking nitisinone, you must not eat foods that are high in tyrosine or phenylalanine, including:

  • chicken, beef, pork, liver, fish, processed meats (bologna, hot dogs, pepperoni, hard sausages), meat tenderizer, herring or other dried fish;

  • cheese, milk, sour cream, yogurt;

  • beer, wine, distilled liquor;

  • avocados, bananas, carrots, potatoes, spinach, tomatoes, raisins, red plums,

  • oatmeal, brown rice,

  • soy sauce, soy protein, tofu, bean curd, garbanzo beans, soy beans, and certain nuts or seeds; or

  • foods that contain an artificial sweetener called aspartame (NutraSweet)--diet soda, some foods labeled as "sugar-free" or "zero calorie."

There are other foods that may contain tyrosine or phenylalanine. Get familiar with the list of foods you must avoid to help control your condition.

Before Using nitisinone

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 nitisinone, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to nitisinone 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.

Pediatric

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

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of nitisinone in the elderly.

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.

Interactions with 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 nitisinone, 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 nitisinone 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.

  • Cyclophosphamide

Interactions with Food/Tobacco/Alcohol

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 nitisinone. 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.

Index Terms

  • NTBC

Administration

Capsules: Administer at least 1 hour prior to, or 2 hours after a meal. Capsules may be opened and contents suspended in a small quantity of water, formula, or apple sauce; administer immediately.

Suspension: Administer without regards to meals. Allow suspension to warm to room temperature (30 to 60 minutes) prior to preparation.

Tablets: Administer without regards to meals. Tablets may be disintegrated in water and administered using an oral syringe or crushed and mixed with applesauce (administration with other liquids or foods is not recommended [has not been studied]). Refer to manufacturer’s labeling for detailed instructions.

Warnings/Precautions

Concerns related to adverse effects:

• Dermatologic effects: Failure to adequately restrict dietary tyrosine and phenylalanine may lead to hyperkeratotic plaques on the soles and palms.

• Hematologic effects: Leukopenia and/or thrombocytopenia have been reported; may improve with dose reduction. May be due to underlying liver disease rather than drug-related (McKiernan 2006). Monitor platelets and WBC regularly during therapy.

• Neurological effects: Failure to adequately restrict dietary tyrosine and phenylalanine may lead to variable degrees of intellectual disability and developmental delay; clinical laboratory assessment including tyrosine levels is recommended for any patient exhibiting abrupt changes in neurological status while on therapy.

• Ocular effects: Failure to adequately restrict dietary tyrosine and phenylalanine may lead to ocular toxicities (eg, conjunctivitis, corneal ulcers, corneal opacities, eye pain, keratitis, photophobia). Slit-lamp examination of the eyes is recommended prior to initiation of therapy and in patients who develop photophobia, eye pain, or signs of inflammation (eg, redness, swelling, burning of the eyes). Immediate measurement of plasma tyrosine concentration is also recommended in patients who develop ocular symptoms.

Dosage form specific issues:

• Glycerol: Oral suspension contains 500 mg/mL of glycerol; oral doses of glycerol ≥10 g may cause headache, upset stomach, and diarrhea. Patients receiving single doses >20 mL are at increased risk for these adverse reactions; consider switching patients unable to tolerate the oral suspension to nitisinone capsules.

Other warnings/precautions:

• Dietary restrictions: Must be used with dietary restriction of tyrosine and phenylalanine; inadequate restriction can result in toxic effects to the eyes, skin, and nervous system. Evaluate plasma tyrosine concentrations in patients who develop signs and symptoms of toxicity. Nutritional consultation is recommended.

Precautions

Consult WARNINGS section for dosing related precautions

Nitisinone Pregnancy Warnings

Animal studies have shown incomplete skeletal ossification of fetal bones (at 0.4 to 20 times the recommended human dose), increased gestational length (at 4 to 20 times the recommended human dose), and decreased offspring survival (at 0.4 times the recommended human dose). In addition, reduced litter size, decreased birth weight, and decreased survival after birth was observed in animals receiving 12 times the recommended clinical dose based on relative body surface area. There are no controlled data in human pregnancy. FDA pregnancy category C: Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.

FDA pregnancy category: C Potential benefit should outweigh the potential risk.

Adverse Effects

>10%

Liver transplantation (13%)

Elevated tyrosine levels (>10%)

1-10%

Liver failure (7%)

Malignant hepatic neoplasm (5%)

Leukopenia (3%)

Thrombocytopenia (3%)

Conjunctivitis (2%)

Corneal opacity (2%)

Keratitis (2%)

Photophobia (2%)

Alopecia (1%)

Blepharitis (1%)

Cataracts (1%)

Dry skin (1%)

Epistaxis (1%)

Exfoliative dermatitis (1%)

Eye pain (1%)

Granulocytopenia (1%)

Maculopapular rash (1%)

Porphyria (1%)

Pruritus (1%)

<1%

Seizure

Brain tumor

Encephalopathy

Hyperkinesia

Cyanosis

Abdominal pain

Diarrhea

Enanthema

Gastrointestinal hemorrhage

Melena

Elevated hepatic enzymes

Liver enlargement hypoglycemia

Septicemia

Bronchitis

Warnings

Contraindications

None

Cautions

Elevated tyrosine and phnylalanine levels may cause developmental delay and hyperkeratotic plaques; maintain plasma level of tyrosine <500 umol/L to avoid toxicity; do not adjust dosage in order to lower plasma tyrosine concentration; restrict dietary intake of tyrosine and phenylalanine

Inadequate restriction of tyrosine and phenylalanine intake can lead to elevations in plasma tyrosine levels; levels > 500 micromol/L may lead to ocular signs and symptoms including corneal ulcers, corneal opacities, keratitis, conjunctivitis, eye pain, and photophobia; a baseline ophthalmologic examination including slit-lamp examination should be considered prior to initiating treatment

Serious adverse effects include severe thrombocytopenia, and leukopenia associated with elevated tyrosine levels; monitor platelet and white blood cell counts; decreasing dose from 1 mg/kg to 0.5 mg/kg twice daily reportedly improved a patient that developed leukopenia and thrombocytopenia in clinical trials; monitor platelet and white blood cell counts

If co-administered with drugs that are metabolized by CYP2C9, additional monitoring may be warranted because of a potential for increased systemic exposure of these drugs

Glycerol content in oral suspension

  • Doses of 20 mL of oral suspension (10 g glycerol) may cause headache, upset stomach and diarrhea due to glycerol content
  • The oral suspension contains 500 mg/mL of glycerol
  • Consider switching patients who are unable to tolerate the oral suspension to the oral capsules (see Administration)
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