KUVAN Frequently Asked Questions
Who will benefit from KUVAN® (sapropterin dihydrochloride)?
In clinical trials with KUVAN Tablets for Oral Use, benefits for PKU patients were observed across the spectrum of PKU phenotypes, including classic PKU. Patients have varying degrees of residual PAH enzyme activity and BH4 responsiveness, so it is not possible to accurately predict the extent of the benefit before administering KUVAN to the patient. A trial of KUVAN is therefore required to determine responsiveness to treatment.1
What are the benefits of taking KUVAN?
KUVAN lowers Phe. In clinical trials with KUVAN in patients with PKU, reductions in blood Phe levels were observed in some patients.1 Although long-term assessment of neurologic function in patients with PKU receiving KUVAN for the treatment of elevated blood Phe has not been fully evaluated, KUVAN may help maintain reduced blood Phe levels as an adjunct to a Phe-restricted diet.
What are the risks of taking KUVAN?
- Hypersensitivity reactions, including anaphylaxis, have occurred
- Monitor patients for signs of gastritis
- Children younger than 7 years of age treated with KUVAN doses of 20 mg/kg per day are at increased risk for low levels of blood Phe, compared with patients 7 years and older
- Active management of dietary Phe intake during KUVAN treatment is required
- Monitor patients for signs of hyperactivity
While the risks for adverse reactions are always present with administration of any medication, the overall incidence of adverse reactions in patients receiving KUVAN in clinical trials was similar to that reported in patients taking placebo. The most common adverse reactions (≥4% of patients) were headache, rhinorrhea, pharyngolaryngeal pain, diarrhea, vomiting, cough, and nasal congestion.
How do I monitor and manage my patient?
KUVAN must be used in combination with a Phe-restricted diet. As with all patients with PKU, dietary Phe intake should be monitored regularly. Baseline blood Phe measurements should be taken just prior to initiation of a KUVAN response test. Patients should be started at a dose of 10 mg/kg per day. To determine whether a patient is benefiting from KUVAN therapy, it is recommended that blood Phe levels be tested after 1 week of KUVAN therapy and periodically for up to 1 month.1 Blood should be collected at the same time of day for each patient. A response to treatment with KUVAN may be determined as a decrease in blood Phe level compared to baseline level.
If sufficient reductions in blood Phe levels do not occur at 10 mg/kg per day, the dose may be increased to 20 mg/kg per day. Patients whose blood Phe does not decrease from baseline after 1 month of treatment at 20 mg/kg per day are non-responders, and treatment with KUVAN should be discontinued in these patients. Doses of KUVAN above 20 mg/kg per day have not been evaluated in clinical trials.
Patients being treated with KUVAN should have frequent blood Phe level measurements and dietary guidance from a dietitian and other members of the healthcare team to ensure maintenance of blood Phe levels in the desirable range.
How is KUVAN administered?
KUVAN should be taken once a day (at the same time each day), preferably with the largest meal of the day.1 KUVAN Powder may be dissolved in water or apple juice or mixed in a small amount of soft food, such as apple sauce or pudding. KUVAN Tablets can be crushed and administered the same way as KUVAN Powder, or can be swallowed whole. Drink or eat the mixture within 30 minutes.
Tablets must be stirred for a few minutes to fully dissolve. If any tablet residue or powder remains in the glass after swallowing, rinse the glass with more liquid for the full dose of KUVAN to be ingested.
How do I calculate the dose of KUVAN?
To calculate the dose of KUVAN, measure the total body weight of your patient. If measured in pounds, divide by 2.2 to determine weight in kilograms. Then multiply the weight in kilograms by the prescribed dosage of KUVAN.
Divide your answer by 100 and round to the closest whole number. KUVAN is offered in 100 mg Tablets and Powder for Oral Solution (as well as a 500 mg powder packet). Dividing your patient’s weight by 100 will yield the number of tablets or 100 mg powder packets of KUVAN to prescribe.
Example for an 80-lb child at the recommended starting dosage of 10 mg/kg per day:
Weight: 80/2.2 = 36.36 kg body weight
Dosing: 36.36 kg x 10 mg/kg = 363.63 mg
Tablet number: 363.63 mg/100 mg = 3.63 → 4 tablets/day
Powder packet number: 363.63 mg/100 mg = 3.63 → four 100 mg packets/day
If the patient’s weight and dosage necessitates at least five 100 mg tablets or packets daily, consider prescribing the KUVAN Powder for Oral Solution 500 mg packet.
Example for a 120-lb individual at 20 mg/kg per day
Weight:120/2.2 = 54.5 kg body weight
Dosing: 54.5 x 20 mg/kg = 1090 mg
100 mg tablet/packet number: Eleven packets or tablets/day
500 mg packet number: Two 500 mg packets + One 100 mg packet
Please see Dosing Card for more information.
What if my patient misses a dose?
A missed dose should be taken as soon as possible, but 2 doses should not be taken on the same day.1 If patients miss a day, they should not double the dose the next day, but skip the missed dose.
What if my patient becomes pregnant?
Because there are no adequate, well-controlled studies of KUVAN in pregnant women, KUVAN should be used during pregnancy only when clearly needed and/or recommended by your physician.1 Women who are exposed to KUVAN during pregnancy are encouraged to enroll in the KUVAN patient registry, called the Phenylketonuria Demographics, Outcomes, and Safety (PKUDOS) Registry.
In maternal PKU syndrome, elevated Phe levels in pregnant women are teratogenic and can cause significant congenital brain and cardiac damage, facial dysmorphism, and growth abnormalities in babies of PKU-affected mothers.2 Patients with PKU who are pregnant or patients with PKU who are considering pregnancy need to obtain appropriately trained medical care to manage their Phe levels rigorously in order to protect their babies from maternal PKU syndrome. The benefits and risks must be weighed on an individual basis.
Will KUVAN continue to work over time?
In clinical trials, the benefit of KUVAN continued throughout the length of the study. KUVAN has been studied for periods from 1 to 164 weeks.1
- KUVAN [package insert]. Novato, CA: BioMarin Pharmaceutical Inc; 2015.
- Scriver CR, Kaufman S. Hyperphenylalaninemia: phenylalanine hydroxylase deficiency. In: Scriver CR, Beaudet AR, Sly WS, et al, eds. The Metabolic and Molecular Bases of Inherited Disease. 8th ed. New York, NY: McGraw-Hill; 2001:1667-1724.