Orfadin Suspension
Name: Orfadin Suspension
- Orfadin Suspension 1 mg
- Orfadin Suspension oral dose
- Orfadin Suspension drug
- Orfadin Suspension adverse effects
- Orfadin Suspension 4mg
- Orfadin Suspension dosage
- Orfadin Suspension how to use
Contraindications
None.
Use in specific populations
Pregnancy
Risk Summary
Limited available data with nitisinone use in pregnant women are not sufficient to determine a drug-associated risk of adverse developmental outcomes. Animal reproduction studies have been conducted for nitisinone. In these studies, nitisinone was administered to mice and rabbits during organogenesis with oral doses of nitisinone up to 20 and 8 times respectively, the recommended initial dose of 1 mg/kg/day. In mice, nitisinone caused incomplete skeletal ossification of fetal bones and decreased pup survival at doses 0.4 times the recommended initial dose, and increased gestational length at doses 4 times the recommended initial dose. In rabbits, nitisinone caused maternal toxicity and incomplete skeletal ossification of fetal bones at doses 1.6 times the recommended initial dose [see Data].
The background risk of major birth defects and miscarriage for the indicated population are unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.
Data
Animal Data
Reproduction studies have been performed in mice at oral doses of about 0.4, 4 and 20 times the recommended initial dose (1 mg/kg/day) and in rabbits at oral doses of about 1.6, 4 and 8 times the recommended initial dose based on the body surface area. In mice, nitisinone has been shown to cause incomplete skeletal ossification of fetal bones at 0.4, 4 and 20 times the recommended initial dose, increased gestational length at 4 and 20 times the recommended initial dose, and decreased pup survival at 0.4 times the recommended initial dose based on the body surface area. In rabbits, nitisinone caused incomplete skeletal ossification of fetal bones at 1.6, 4 and 8 times the recommended initial dose based on the body surface area.
Lactation
Risk Summary
There are no data on the presence of nitisinone in human milk, the effects on the breastfed infant, or the effects on milk production. Data suggest that nitisinone is present in rat milk due to findings of ocular toxicity and lower body weight seen in drug naive nursing rat pups. The development and health benefits of breastfeeding should be considered along with the mother's clinical need for ORFADIN and any potential adverse effects on the breastfed infant from ORFADIN or from the underlying maternal condition.
Pediatric Use
The safety and effectiveness of ORFADIN have been established in pediatric patients for the treatment of HT-1 in combination with dietary restriction of tyrosine and phenylalanine. Use of ORFADIN in pediatric patients is supported by evidence from one open-label, uncontrolled clinical study conducted in 207 patients with HT-1 ages 0 to 22 years (median age 9 months) [see Clinical Studies (14)].
Geriatric Use
Clinical studies of nitisinone did not include any subjects aged 65 and over. No pharmacokinetic studies of nitisinone have been performed in geriatric patients. In general, dose selection for an elderly patient should be cautious reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and concomitant disease or other drug therapy in this patient population.
Patient Counseling Information
Advise the patient to read the FDA-approved patient labeling (Instructions for Use).
Preparation and Administration Instructions [see Dosage and Administration (2.2)]
Preparation of the Oral Suspension
The oral suspension will be dispensed with an oral syringe of appropriate size and a bottle adaptor provided by a pharmacist or other healthcare provider.
Preparing a Bottle Without the Adapter Already Inserted:
- Store the bottle in the refrigerator prior to first use.
- Remove the bottle from the refrigerator. Calculate 60 days from when the bottle is removed from the refrigerator. Write this date as the “Discard after” date on the bottle label.
- Allow the bottle to warm to room temperature (30 to 60 minutes).
- Shake the bottle vigorously for at least 20 seconds until the solid cake at the bottom of the bottle is completely dispersed. Check that there are no particles left at the bottom of the bottle. Foam will form in the bottle.
- Insert the bottle adapter.
Preparing a Bottle With the Adapter Inserted:
- Shake the bottle vigorously for at least 5 seconds. Check that there are no particles left at the bottom of the bottle. Foam will form in the bottle.
Measuring and Administering the Dose
Once the bottle is prepared with the adapter:
- Use the oral syringe to measure the dose.
- Keep the bottle upright and insert the oral syringe into the adapter.
- Carefully turn the bottle upside down with the oral syringe in place. Wait for the foam to rise to the top of the bottle.
- Pull back on the syringe plunger to withdraw the dose.
- Leave the syringe in the adapter and turn the bottle upright.
- Remove the syringe from the adapter by gently twisting it out of the bottle.
- Dispense the dose into the patient's mouth.
- Do not remove the bottle adapter.
- Store the bottle at room temperature (not above 25°C).
Administration of ORFADIN Capsules and Oral Suspension
- Maintain dietary restriction of tyrosine and phenylalanine when taking ORFADIN.
- Capsules: Take at least one hour before, or two hours after a meal. For patients who have difficulty swallowing the capsules and for which the oral suspension is not suitable [see Warnings and Precautions (5.3]), the capsules may be opened and the contents suspended in a small amount of water, formula or apple sauce immediately before use. Or, the oral suspension may be used instead.
- Oral suspension: Take without regard to meals.
Elevated Plasma Tyrosine Levels, Ocular Symptoms, Developmental Delay and Hyperkeratotic Plaques
- Inform patients that inadequate restriction may be associated with ocular signs and symptoms, intellectual disability and developmental delay, and painful hyperkeratotic plaques on the soles and palms. Advise patients and caregivers of the need to maintain dietary restriction of tyrosine and phenylalanine and to report any unexplained ocular, neurologic, or other symptoms promptly to their healthcare provider [see Warnings and Precautions (5.1)].
Risk of Adverse Reactions Due to Glycerol Content of ORFADIN Oral Suspension
Advise patients receiving doses of greater than 20 mL of ORFADIN oral suspension that they may experience headache, upset stomach and diarrhea due to the glycerol component of the formulation and if they develop symptoms to report these to their healthcare provider [see Warnings and Precautions (5.3)].
Manufactured by:
Apotek Produktion & Laboratorier AB, Sweden
Marketed by:
Sobi, Inc
890 Winter Street
Waltham, MA 02451
Instructions for Use
ORFADIN (OR-fuh-din)
(nitisinone)
oral suspension
4 mg/mL
Read this Instructions for Use before you start taking ORFADIN oral suspension and each time you get a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or your treatment.
Important information about measuring ORFADIN oral suspension:
- Use the oral syringe provided with your ORFADIN oral suspension to make sure you measure the right amount.
- You will be provided with:
- 1 bottle of ORFADIN oral suspension
- 1 oral syringe
- 1 adapter (The adapter may or may not be inserted in your bottle of ORFADIN oral suspension when you receive it.)
Figure A
If the adapter is not inserted in your bottle of ORFADIN oral suspension when you receive it, follow the instructions in “How to prepare a bottle of ORFADIN oral suspension if the adapter is not inserted.”
If the adapter is inserted in your bottle of ORFADIN oral suspension when you receive it, follow the instructions in “How to prepare a dose of ORFADIN oral suspension after the adapter is inserted.”
How to prepare a bottle of ORFADIN oral suspension if the adapter is not inserted:
See “How should I store ORFADIN oral suspension?” for instructions on how to store ORFADIN oral suspension if the adapter is not inserted.
1. Remove the ORFADIN oral suspension bottle from the refrigerator 30 minutes to 1 hour before using it to allow it to reach room temperature.ORFADIN oral suspension should be thrown away (discarded) 60 days after it is removed from the refrigerator and the adapter is inserted in the bottle. Write the discard date on the bottle label.
| 2. Shake the bottle well for at least 20 seconds until the solid cake of particles at the bottom of the bottle is dissolved (See Figure B). Check that there are no particles left at the bottom of the bottle. Foam will form in the bottle. | Figure B |
| 3. Remove the child resistant screw cap by pushing it down firmly and turning it counter-clockwise (See Figure C). | Figure C |
| 4. Place the open bottle upright on a flat surface. Push the ribbed end of the adapter firmly into the neck of the bottle as far as it will go (See Figure D). Replace the child resistant screw cap on the bottle. Do not remove the adapter from the bottle after it is inserted. | Figure D |
How to prepare a dose of ORFADIN oral suspension after the adapter is inserted
See “How should I store ORFADIN oral suspension?” for instructions on how to store ORFADIN oral suspension after the adapter is inserted.
| 1. Shake the ORFADIN oral suspension bottle well for at least 5 seconds (See Figure E). Check that there are no particles left at the bottom of the bottle. Foam will form in the bottle. | Figure E |
| 2. Remove the child resistant screw cap right away by pushing it down firmly and turning it counter-clockwise (See Figure F). | Figure F |
| 3. Hold the oral syringe in one hand. With your other hand, fully push down (depress) the plunger (See Figure G). | Figure G |
| 4. Keeping the bottle in an upright position, insert the oral syringe firmly into the adapter (See Figure H). | Figure H |
| 5. Carefully turn the bottle upside down with the oral syringe in place (See Figure I). Wait until you can see that the foam is at the top of the bottle to avoid withdrawing bubbles into the syringe. | Figure I |
| 6. Pull back slowly on the oral syringe plunger until the top edge of the black ring is at the line marking the dose prescribed by your healthcare provider (See Figure J). Figure J shows a dose of 1 mL as an example. If you see air bubbles in the oral syringe, fully push in the plunger so that the oral suspension flows back into the bottle. Then, withdraw your prescribed dose of oral suspension. | Figure J |
| 7. Leave the oral syringe in the adapter and turn the bottle to an upright position. Place the bottle onto a flat surface. Remove the oral syringe by gently twisting it out of the bottle (See Figure K). Do not pull straight up on the syringe to remove it from the bottle because this can cause the adapter to come out of the bottle. | Figure K |
| 8. Place the oral syringe in your mouth right away. Slowly push on the plunger until the oral syringe is empty. See Figure L). | Figure L |
| 9. Leave the adapter in the bottle. Put the child resistant screw cap back on the bottle (See Figure M). | Figure M |
- Talk to your healthcare provider or pharmacist if you have questions about how to use the oral syringe or if you lose the oral syringe.
How should I store ORFADIN oral suspension?
- Store the ORFADIN oral suspension bottle in an upright position. Keep the oral syringe with your medicine.
Before the adapter is inserted into the bottle:
- If the adapter has not been inserted into the bottle, store ORFADIN oral suspension in the refrigerator between 36°F to 46°F (2°C to 8°C).
- Do not freeze ORFADIN oral suspension.
After the adapter is inserted into the bottle:
- After the adapter has been inserted into the bottle, store ORFADIN oral suspension at room temperature, 77°F (25°C) or below.
- Throw away (discard) ORFADIN oral suspension 60 days after the adapter is inserted in the bottle. You or your pharmacist should write the discard date on the bottle label.
What are the ingredients in ORFADIN oral suspension?
Active ingredient: nitisinone
Inactive ingredients: hydroxypropyl methylcellulose, glycerol, polysorbate 80, sodium benzoate, citric acid monohydrate, trisodium citrate dihydrate, strawberry aroma (artificial) and purified water
This Instructions for Use has been approved by the U.S. Food and Drug Administration.
Manufactured by:
Apotek Produktion & Laboratorier AB, Sweden
Marketed by:
Sobi, Inc
890 Winter Street
Waltham, MA 02451
© Swedish Orphan Biovitrum AB (publ). All rights reserved.
Issued: Month/Year
Principal Display Panel - 4mg/ml Carton Label
Orfadin®
(nitisinone)
oral suspension
4 mg/ml
For Oral Use.
Rx only.
Shake well for 20 seconds before
first use. Shake well for 5 seconds
before each use.
90 ml
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| Labeler - Swedish Orphan Biovitrum AB (publ) (354010589) |