Who will benefit from KUVAN?
What are the benefits of taking KUVAN?
What are the risks of taking KUVAN?
How do I monitor and manage my patient?
How is KUVAN administered?
How do I calculate the dose of KUVAN?
What if my patient misses a dose?
What if my patient becomes pregnant?
Will KUVAN continue to work over time?

Who will benefit from KUVAN?

In clinical trials with KUVAN, benefits for PKU patients were observed across the spectrum of PKU phenotypes, including classic PKU. Because patients have varying degrees of residual PAH enzyme activity and BH4 responsiveness, it is not possible to accurately predict the extent of the benefit before administering KUVAN to the patient.¹ Generally, patients with residual PAH enzyme activity may benefit from taking KUVAN.

Over 528 mutations in the PAH gene are known to cause PKU or HPA.²⁷ However, for most patients, genotype has not been shown to clearly identify BH4 response.²⁸ Therefore, PKU patients should receive a trial of KUVAN in order to determine responsiveness to treatment.¹

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What are the benefits of taking KUVAN?¹

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 assessed, KUVAN may help maintain reduced blood Phe levels as an adjunct to a Phe-restricted diet.

Prolonged high blood Phe levels are neurotoxic and lead to impairment of intelligence and other brain functions as well as behavioral issues (such as attentiveness).¹ Reduction of blood Phe levels through dietary control is an important determinant of long-term cognitive outcome in PKU patients, and reduction of blood Phe levels in patients with PKU has been shown to decrease the long-term risk of cognitive impairment.⁴ However, it is difficult for many patients to maintain reduced blood Phe through the Phe-restricted diet, and many patients with PKU experience some cognitive deficits despite efforts to maintain dietary Phe control.^2,5,8,10

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What are the risks of taking KUVAN?¹

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 treated with KUVAN) across all studies (n=579) were headache, diarrhea, abdominal pain, upper respiratory tract infection, pharyngolaryngeal pain, vomiting, and nausea.

Another important consideration is that response to KUVAN treatment in PKU patients may be variable and blood Phe levels should be monitored closely. Not all patients responded to treatment with KUVAN in clinical trials, as determined by routine monitoring of blood Phe levels. Prolonged Phe elevations can result in neurologic impairment. Conversely, some patients in clinical trials who were following Phe-restricted diets and received treatment with KUVAN experienced substantial reductions of blood Phe. Levels of blood Phe that are too low may be associated with catabolism and protein breakdown. Therefore, patients taking KUVAN should be monitored closely to ensure that blood Phe levels are not too low, and, if necessary, the dose of KUVAN should be adjusted.

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How do I monitor and manage my patient?¹

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/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/day, the dose may be increased to 20 mg/kg/day. Patients whose blood Phe does not decrease from baseline after 1 month of treatment at 20 mg/kg/day are non-responders, and treatment with KUVAN should be discontinued in these patients. Doses of KUVAN above 20 mg/kg/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.

Fever and illness can cause decreased caloric intake and lead to endogenous protein breakdown (catabolism of protein). Phe derived from this endogenous protein breakdown can cause a transient rise of the blood Phe level. The physician and dietitian can suggest changes in treatment to help maintain blood Phe levels in the desirable range during illness.

Please see DOSING AND ADMINISTRATION for more information.

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How is KUVAN administered?¹

KUVAN should be administered once a day, and it is recommended that the patient take it at the same time each day with a meal to obtain effective 24-hour Phe control. Patients should dissolve the tablets in 4–8 oz of water or apple juice. Tablets must be stirred for a few minutes to fully dissolve; after swallowing, the glass should be rinsed with more liquid for the full dose of KUVAN to be ingested. Please see DOSING AND ADMINISTRATION for more information.

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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 because KUVAN comes in 100-mg tablets, and round to the closest whole number. This is the number of tablets of KUVAN to prescribe.

Example for an 80-lb child at the recommended starting dosage of 10 mg/kg/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

Please see DOSING CARD for more information.

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What if my patient misses a dose?¹

A missed dose should be taken as soon as possible, but 2 doses should not be taken on the same day.

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What if my patient becomes pregnant?¹

Because there are no adequate, well-controlled studies of KUVAN in pregnant women, KUVAN should be used during pregnancy only if clearly needed. 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.⁴ Pregnant PKU patients or PKU patients 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.

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Will KUVAN continue to work over time?¹

In clinical trials, the benefit of KUVAN continued throughout the length of the study. KUVAN has been studied for periods from 1 to 30 weeks.

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