July 30, 2016
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Kuvan Side Effects Center

Medical Editor: John P. Cunha, DO, FACOEP

Last reviewed on RxList 5/6/2016

Kuvan (saproterin dihydrochloride tablets) is a synthetic form of a natural salt that contributes to the function of a certain enzyme in the body used to help the body activate the enzyme needed to control blood levels of phenylalanine. Kuvan is used in people with phenylketonuria (PKU). Common side effects of Kuvan include:

  • nausea
  • vomiting
  • stomach pain
  • diarrhea
  • runny or stuffy nose
  • cough
  • headache
  • flushing
  • agitation
  • fidgeting
  • dizziness, or
  • joint pain

The recommended starting dose of Kuvan is 10 mg/kg/day taken once daily. Kuvan may interact with levodopa, methotrexate, sildenafil, tadalafil, or vardenafil. Tell your doctor all medications and supplements you use. During pregnancy, Kuvan should be used only when prescribed. It may be harmful to a fetus. It is unknown if this drug passes into breast milk or if it could harm a nursing baby. Consult your doctor before breastfeeding.

Our Kuvan (saproterin dihydrochloride) Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

What is Patient Information in Detail?

Easy-to-read and understand detailed drug information and pill images for the patient or caregiver from Cerner Multum.

Kuvan in Detail - Patient Information: Side Effects

If sapropterin is not controlling your condition properly, you may have symptoms such as behavior changes, numbness or tingling, or problems with speech, vision, or balance. Call your doctor right away if you have any of these symptoms.

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have any of the serious side effects below:

  • seizure (convulsions);
  • chest pain or heavy feeling, pain spreading to the arm or shoulder, general ill feeling;
  • easy bruising or bleeding;
  • fever, chills, body aches, flu symptoms;
  • swelling in your hands or feet;
  • pain or burning when you urinate;
  • weakness or fainting;
  • black, bloody, or tarry stools; or
  • coughing up blood or vomit that looks like coffee grounds.

Less serious side effects may include:

  • nausea, vomiting, stomach pain, diarrhea;
  • runny or stuffy nose, cough;
  • headache, feeling agitated;
  • dizziness; or
  • joint pain.

This is not a complete list of side effects and others may occur. Tell your doctor about any unusual or bothersome side effect. You may report side effects to FDA at 1-800-FDA-1088.

Read the entire detailed patient monograph for Kuvan (Saproterin Dihydrochloride Tablets)

What is Prescribing information?

The FDA package insert formatted in easy-to-find categories for health professionals and clinicians.

Kuvan FDA Prescribing Information: Side Effects
(Adverse Reactions)


Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reactions rates observed in the clinical trials of a drug cannot be directly compared to the rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

PKU Clinical Studies

The safety of Kuvan was evaluated in 6 clinical studies in patients with PKU (aged 1 month to 50 years) [see Clinical Studies].

In Studies1-4 (controlled and uncontrolled studies), 579 patients with PKU aged 4 to 49 years received Kuvan in doses ranging from 5 to 20 mg/kg per day for lengths of treatment ranging from 1 to 164 weeks. The patient population was evenly distributed in gender, and approximately 95% of patients were Caucasian. The most common adverse reactions (≥4% of patients) were headache, rhinorrhea, pharyngolaryngeal pain, diarrhea, vomiting, cough, and nasal congestion.

The data described in Table 3 reflect exposure of 74 patients with PKU to Kuvan at doses of 10 to 20 mg/kg per day for 6 to 10 weeks in two double-blind, placebo-controlled clinical trials (Studies 2 and 4).

Table 3 enumerates adverse reactions occurring in at least 4% of patients treated with Kuvan in the double-blind, placebo-controlled clinical trials described above.

Table 3: Summary of Adverse Reactions Occurring in ≥4% of Patients in Placebo-Controlled Clinical Studies with Kuvan

MedDRA Preferred Term Treatment
No. Patients (%) No. Patients (%)
Headache 11 (15) 8 (14)
Rhinorrhea 8 (11) 0
Pharyngolaryngeal pain 7(10) 1 (2)
Diarrhea 6 (8) 3 (5)
Vomiting 6 (8) 4 (7)
Cough 5 (7) 3 (5)
Nasal congestion 3 (4) 0

In open-label, uncontrolled clinical trials (Studies 1 and 3) all patients received Kuvan in doses of 5 to 20 mg/kg per day, adverse reactions were similar in type and frequency to those reported in the double-blind, placebo-controlled clinical trials [see Clinical Studies].

In Study 5, 65 pediatric patients with PKU aged 1 month to 6 years received Kuvan 20 mg/kg per day for 6 months. Adverse reactions in these patients were similar in frequency and type as those seen in other Kuvan clinical trials except for an increased incidence of low Phe levels. Twenty-five percent (16 out of 65) of patients developed Phe levels below normal for age [see WARNINGS AND PRECAUTIONS), Pediatric Use (8.4), and Clinical Studies (14.1)].

In Study 6, a long term, open-label, extension study of 111 patients aged 4 to 50 years, receiving Kuvan in doses ranging from 5 to 20 mg/kg per day, adverse reactions were similar in type and frequency to those reported in the previous clinical studies. Fifty-five patients received Kuvan both as dissolved and intact tablets. There were no notable differences in the incidence or severity of adverse reactions between the two methods of administration. The mean (± SD) exposure to sapropterin for the entire study population was 659 ± 221 days (maximum 953 days).

Safety Experience From Clinical Studies For Non-PKU Indications

Approximately 800 healthy volunteers and patients with disorders other than PKU, some of whom had underlying neurologic disorders or cardiovascular disease, have been administered a different formulation of the same active ingredient (sapropterin) in approximately 19 controlled and uncontrolled clinical trials. In these clinical trials, subjects were administered sapropterin at doses ranging from 1 to 100 mg/kg per day for lengths of exposure from 1 day to 2 years.

Serious and severe adverse reactions (regardless of causality) during sapropterin administration were convulsions, exacerbation of convulsions [see WARNINGS AND PRECAUTIONS], dizziness, gastrointestinal bleeding, post-procedural bleeding, headache, irritability, myocardial infarction, overstimulation, and respiratory failure. Common adverse reactions were headache, peripheral edema, arthralgia, polyuria, agitation, dizziness, nausea, pharyngitis, abdominal pain, upper abdominal pain, and upper respiratory tract infection.

Post-Marketing Experience

The following adverse reactions have been identified during post-approval use of Kuvan. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish causal relationship to drug exposure.

In worldwide marketing experience, the most common adverse reactions due to Kuvan are oropharyngeal pain, pharyngitis, esophageal pain, gastritis, dyspepsia, abdominal pain, nausea and vomiting. Hypersensitivity reactions including anaphylaxis and rash have been reported. Most hypersensitivity reactions occurred within several days of initiating treatment. Two cases of hyperactivity have been reported, including one case in a patient who received an accidental overdose of Kuvan [see WARNINGS AND PRECAUTIONS].

Read the entire FDA prescribing information for Kuvan (Saproterin Dihydrochloride Tablets)

Report Problems to the Food and Drug Administration


You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.

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