Kuvan (Saproterin Dihydrochloride Tablets)
برای این دارو، اطلاعات عمومی (فارسی) یافت نشد . برای افزودن اطلاعات فارسی به این دارو کلیک نمایید.
Kuvan (Saproterin Dihydrochloride Tablets)

Kuvan
(sapropterin dihydrochloride) Tablets

DRUG DESCRIPTION

Sapropterin dihydrochloride, the active pharmaceutical ingredient in Kuvan (saproterin dihydrochloride tablets) Tablets, is a synthetic preparation of the dihydrochloride salt of naturally occurring tetrahydrobiopterin (BH4). Sapropterin dihydrochloride is an off-white to light yellow crystals or crystalline powder.

The chemical name of sapropterin dihydrochloride is (6R)-2-amino-6-[(1R,2S)-1,2- dihydroxypropyl]-5,6,7,8-tetrahydro-4(1H)-pteridinone dihydrochloride and the molecular formula is C9H15N5O3·2HCl with a molecular weight of 314.17.

Sapropterin dihydrochloride has the following structural formula:

Kuvan (sapropterin dihydrochloride) structural formula illustration

Each Kuvan Tablet contains 100 mg of sapropterin dihydrochloride (equivalent to 76.8 mg of sapropterin base). Tablets are round, off-white to light yellow, mottled, and debossed with “177”. Each tablet contains the following inactive ingredients: ascorbic acid (USP), crospovidone (NF), dibasic calcium phosphate (USP), D-mannitol (USP), riboflavin (USP), and sodium stearyl fumarate (NF).

What are the possible side effects of sapropterin (Kuvan)?

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...

Read All Potential Side Effects and See Pictures of Kuvan »

Last reviewed on RxList: 1/3/2008
This monograph has been modified to include the generic and brand name in many instances.

INDICATIONS

Kuvan (saproterin dihydrochloride tablets) is indicated to reduce blood phenylalanine (Phe) levels in patients with hyperphenylalaninemia (HPA) due to tetrahydrobiopterin- (BH4-) responsive Phenylketonuria (PKU). Kuvan (saproterin dihydrochloride tablets) is to be used in conjunction with a Phe-restricted diet.

DOSAGE AND ADMINISTRATION

Dosage

The recommended starting dose of Kuvan (saproterin dihydrochloride tablets) is 10 mg/kg/day taken once daily.

Response to therapy is determined by change in blood Phe following treatment with Kuvan (saproterin dihydrochloride tablets) at 10 mg/kg/day for a period of up to 1 month. Blood Phe levels should be checked after 1 week of Kuvan (saproterin dihydrochloride tablets) treatment and periodically for up to a month. If blood Phe does not decrease from baseline at 10 mg/kg/day, the dose may be increased to 20 mg/kg/day. Patients whose blood Phe does not decrease after 1 month of treatment at 20 mg/kg/day are non-responders, and treatment with Kuvan (saproterin dihydrochloride tablets) should be discontinued in these patients.

Once responsiveness to Kuvan (saproterin dihydrochloride tablets) has been established, the dosage may be adjusted within the range of 5 to 20 mg/kg/day according to response to therapy. Doses of Kuvan (saproterin dihydrochloride tablets) above 20 mg/kg/day have not been evaluated in clinical trials.

Administration

Kuvan (sapropterin dihydrochloride) Tablets should be administered orally with food to increase absorption, preferably at the same time each day. Kuvan (saproterin dihydrochloride tablets) Tablets should be dissolved in 4 to 8 oz. (120 to 240 mL) of water or apple juice and taken within 15 minutes of dissolution. It may take a few minutes for the tablets to dissolve. To make the tablets dissolve faster, stir or crush them. The tablets may not dissolve completely. Patients may see small pieces floating on top of the water or apple juice. This is normal and safe for patients to swallow. If after drinking the medicine patients still see pieces of the tablet, they can add more water or apple juice to make sure that they take all of the medicine. A missed dose should be taken as soon as possible, but 2 doses should not be taken on the same day.

HOW SUPPLIED

Dosage Forms And Strengths

Kuvan (sapropterin dihydrochloride) Tablets are unscored, uncoated, immediate-release tablets for oral use. Each tablet contains 100 mg of sapropterin dihydrochloride (equivalent to 76.8 mg of sapropterin base). Tablets are round, off-white to light yellow, mottled, and debossed with “177”.

Kuvan (sapropterin dihydrochloride) Tablets are supplied in high-density polyethylene bottles, sealed with aluminized film, and closed with child-resistant caps. Each bottle contains 120 tablets, a silica gel desiccant cartridge, and a pharmaceutical-grade polyester coil. Each Kuvan Tablet contains 100 mg of sapropterin dihydrochloride (equivalent to 76.8 mg of sapropterin base).

Bottle of 120 tablets..............................NDC 68135-300-02

Storage

Store at 20°C to 25°C (68-77°F); excursions allowed between 15°C to 30°C (59-86°F) [see USP Controlled Room Temperature]. Keep container tightly closed. Protect from moisture.

Manufactured for: BioMarin Pharmaceutical Inc. Novato, CA 94949 Manufactured by: Lyne Laboratories, Inc. Brockton, MA 02301. FDA Rev date: 12/13/2007

Last reviewed on RxList: 1/3/2008
This monograph has been modified to include the generic and brand name in many instances.

SIDE EFFECTS

Clinical Trials Experience in PKU

In clinical trials, Kuvan (saproterin dihydrochloride tablets) has been administered to 579 patients with PKU in doses ranging from 5 to 20 mg/kg/day for lengths of treatment ranging from 1 to 30 weeks. Patients were aged 4 to 49 years old. The patient population was nearly evenly distributed in gender, and approximately 95% of patients were Caucasian.

The most serious adverse reactions during Kuvan (saproterin dihydrochloride tablets) administration (regardless of relationship to treatment) were gastritis, spinal cord injury, streptococcal infection, testicular carcinoma, and urinary tract infection. Mild to moderate neutropenia was noted during Kuvan (saproterin dihydrochloride tablets) administration in 24 of 579 patients (4%). The most common ( ≥ 4% of patients treated with Kuvan (saproterin dihydrochloride tablets) ) across all studies (n=579) were headache, diarrhea, abdominal pain, upper respiratory tract infection, pharyngolaryngeal pain, vomiting, and nausea.

The data described below reflect exposure of 74 patients with PKU to Kuvan (saproterin dihydrochloride tablets) at doses of 10 to 20 mg/kg/day for 6 to 10 weeks in 2 double-blind, placebo-controlled clinical trials. The overall incidence of adverse reactions in patients receiving Kuvan (saproterin dihydrochloride tablets) was similar to that reported with patients receiving placebo.

Because clinical trials were conducted under varying conditions, the observed adverse reaction rates may not predict the rates observed in patients in clinical practice. Table 1 enumerates treatment-emergent adverse reactions (regardless of relationship) that occurred in at least 4% of patients treated with Kuvan (saproterin dihydrochloride tablets) in the double-blind, placebo-controlled clinical trials described above. Reported frequency of adverse reactions was classified by MedDRA terms (Table 1).

Table 1: Summary of Adverse Reactions by Preferred Term Occurring in ≥ 4% of Patients in Controlled Clinical Studies With Kuvan (saproterin dihydrochloride tablets)

  Treatment
Kuvan Placebo
Patients Treated N = 74 N = 59
Preferred Term N (%) N (%)
Any Adverse Reaction 47 (64) 42 (71)
Headache 11 (15) 8 (14)
Upper respiratory tract infection 9 (12) 14 (24)
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)
Pyrexia 5 (7) 4 (7)
Contusion 4 (5) 1 (2)
Abdominal pain 4 (5) 5 (8)
Rash 4 (5) 4 (7)
Nasal congestion 3 (4) 0

In open-label, uncontrolled clinical trials in which all patients received Kuvan (saproterin dihydrochloride tablets) in doses of 5 to 20 mg/kg/day, adverse reactions were similar in type and frequency to those reported in the double-blind, placebo-controlled clinical trials.

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 20 mg/kg/day for lengths of exposure from 1 day to 2 years. Serious and severe adverse reactions (regardless of relationship) 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, and upper respiratory tract infection.

Post-Marketing Experience

The following adverse reactions have been identified during a 10-year post-approval safety surveillance program in Japan of another formulation of the same active ingredient (sapropterin). This safety surveillance program was conducted in 30 patients, 27 of whom had disorders other than PKU and had an underlying neurologic condition. The most common adverse reactions were convulsions and exacerbation of convulsions in 3 of the non-PKU patients [see Warnings and PRECAUTIONS], and increased gamma-glutamyltransferase (GGT) in 2 of the non-PKU patients.

Read the Kuvan (saproterin dihydrochloride tablets) Side Effects Center for a complete guide to possible side effects »

DRUG INTERACTIONS

No drug interaction studies were performed.

Last reviewed on RxList: 1/3/2008
This monograph has been modified to include the generic and brand name in many instances.

WARNINGS

Included as part of the PRECAUTIONS section.

PRECAUTIONS

Monitor Blood Phe Levels During Treatment

Treatment with Kuvan (saproterin dihydrochloride tablets) should be directed by physicians knowledgeable in the management of PKU. Prolonged elevations in blood Phe levels in patients with PKU can result in severe neurologic damage, including severe mental retardation, microcephaly, delayed speech, seizures, and behavioral abnormalities. This may occur even if patients are taking Kuvan (saproterin dihydrochloride tablets) but not adequately controlling their blood Phe levels within recommended target range. Long-term studies of neurocognitive outcomes with Kuvan (saproterin dihydrochloride tablets) treatment have not been conducted. Conversely, prolonged levels of blood Phe that are too low have been associated with catabolism and protein breakdown. Active management of dietary Phe intake while taking Kuvan (saproterin dihydrochloride tablets) is required to ensure adequate Phe control and nutritional balance.

Identify Non-Responders to Kuvan (saproterin dihydrochloride tablets) Treatment

Not all patients with PKU respond to treatment with Kuvan (saproterin dihydrochloride tablets) . In clinical trials, approximately 20% to 56% of PKU patients responded to treatment with Kuvan [see Clinical Studies]. Response to treatment cannot be pre-determined by laboratory testing (e.g., genetic testing), and can only be determined by a therapeutic trial of Kuvan [see DOSAGE AND ADMINISTRATION].

Treat All Patients With a Phe-restricted Diet

Patients with PKU who are being treated with Kuvan (saproterin dihydrochloride tablets) should also be treated with a Phe-restricted diet. The initiation of Kuvan (saproterin dihydrochloride tablets) therapy does not eliminate the need for appropriate monitoring by trained professionals to assure that blood Phe control is maintained in the context of ongoing dietary management.

Use With Caution in Patients With Hepatic Impairment

Patients with liver impairment have not been evaluated in clinical trials with Kuvan (saproterin dihydrochloride tablets) . Patients who have liver impairment should be carefully monitored when receiving Kuvan (saproterin dihydrochloride tablets) because hepatic damage has been associated with impaired Phe metabolism.

Monitor for Allergic Reactions

Patients who have a known severe allergy to any of the components of Kuvan (saproterin dihydrochloride tablets) should not take Kuvan (saproterin dihydrochloride tablets) . In clinical trials conducted with Kuvan (saproterin dihydrochloride tablets) , no severe allergic reactions were observed. The risks and benefits of continued treatment with Kuvan (saproterin dihydrochloride tablets) in patients with mild to moderate allergic reactions (such as rash) should be considered.

Use With Caution When Co-administering Kuvan (saproterin dihydrochloride tablets) and Medications Known to Inhibit Folate Metabolism

Drugs known to affect folate metabolism (e.g., methotrexate) and their derivatives should be used with caution while taking Kuvan (saproterin dihydrochloride tablets) because these drugs can decrease BH4 levels by inhibiting the enzyme dihydropteridine reductase (DHPR).

Use With Caution When Co-administering Kuvan (saproterin dihydrochloride tablets) and Drugs Known to Affect Nitric Oxide-Mediated Vasorelaxation

Caution should be used with the administration of Kuvan (saproterin dihydrochloride tablets) to patients who are receiving drugs that affect nitric oxide-mediated vasorelaxation (e.g., PDE-5 inhibitors such as sildenafil, vardenafil, or tadalafil), because both sapropterin dihydrochloride and PDE-5 inhibitors may induce vasorelaxation. The additive effect of sapropterin and PDE-5 inhibitor co-administration could lead to a reduction in blood pressure; however, the combined use of these medications has not been evaluated in humans. In animal studies, orally administered Kuvan (saproterin dihydrochloride tablets) in combination with a PDE-5 inhibitor had no effect on blood pressure.

Use With Caution When Co-administering Kuvan (saproterin dihydrochloride tablets) and Levodopa

Caution should be used with the administration of Kuvan (saproterin dihydrochloride tablets) to patients who are receiving levodopa. In a 10-year post-marketing safety surveillance program for a non-PKU indication using another formulation of the same active ingredient (sapropterin), 3 patients with underlying neurologic disorders experienced convulsions, exacerbation of convulsions, over-stimulation, or irritability during co-administration of levodopa and sapropterin.

Patient Counseling Information

See FDA-Approved Patient Information Labeling

Patients should be advised of the following information before beginning treatment with Kuvan (saproterin dihydrochloride tablets) :

Important Information to Consider Prior to Prescribing Kuvan (saproterin dihydrochloride tablets)

Patients with residual PAH enzyme activity may benefit from taking Kuvan (saproterin dihydrochloride tablets) ; however, not all patients with PKU respond to treatment with Kuvan (saproterin dihydrochloride tablets) . In clinical trials, approximately 20% to 56% of PKU patients responded to treatment with Kuvan (saproterin dihydrochloride tablets) , and reductions in blood Phe levels were observed in patients across the continuum of PKU phenotypes (mild, moderate, and severe PKU).

Since patients have varying degrees of residual PAH enzyme activity and BH4 responsiveness, it is not possible to accurately predict the extent of response before administering Kuvan (saproterin dihydrochloride tablets) to the patient, and response to treatment cannot be pre-determined by laboratory testing (e.g., genetic testing). Response to Kuvan (saproterin dihydrochloride tablets) can only be determined by a therapeutic trial.

To determine if a patient may respond to treatment with Kuvan (saproterin dihydrochloride tablets) , the patient must be treated with Kuvan (saproterin dihydrochloride tablets) and evaluated for changes in blood Phe. Blood Phe levels and dietary Phe intake should be measured frequently [see Warnings and PRECAUTIONS].

Blood Phe Monitoring and Management

Treatment with Kuvan (saproterin dihydrochloride tablets) should be directed by physicians knowledgeable in the management of PKU, and the initiation of Kuvan (saproterin dihydrochloride tablets) therapy does not eliminate the need for appropriate monitoring by trained professionals. Patients being treated with Kuvan (saproterin dihydrochloride tablets) should have frequent blood Phe measurements and nutritional counseling with their physician and other members of the health care team to ensure maintenance of blood Phe levels in the desirable range.

Since changes in dietary Phe intake can obscure the effect of Kuvan (saproterin dihydrochloride tablets) on blood Phe levels, and since not all patients will respond to treatment with Kuvan (saproterin dihydrochloride tablets) , all patients with PKU should be treated with a Phe-restricted diet in addition to treatment with Kuvan (saproterin dihydrochloride tablets) [see Warnings and PRECAUTIONS].

To determine if a patient responds to Kuvan (saproterin dihydrochloride tablets) therapy, patients must not modify their existing dietary Phe intake during the evaluation period in order to get an accurate assessment of the effect of Kuvan (saproterin dihydrochloride tablets) on blood Phe levels. Baseline blood Phe measurements should be taken just prior to initiation of a Kuvan (saproterin dihydrochloride tablets) response test. Patients should be started at a dose of 10 mg/kg/day. Blood Phe levels should be checked after 1 week of Kuvan (saproterin dihydrochloride tablets) treatment and periodically for up to a month to determine response. A response to treatment with Kuvan (saproterin dihydrochloride tablets) may be determined by a decrease in blood Phe level compared to baseline level. If blood Phe level does not decrease 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 [see DOSAGE AND ADMINISTRATION].

For patients who respond to Kuvan (saproterin dihydrochloride tablets) treatment, the dosage may be adjusted within the range of 5 to 20 mg/kg/day according to response to therapy. Doses above 20 mg/kg/day have not been evaluated in clinical trials.

After the dose of Kuvan (saproterin dihydrochloride tablets) has been established, continued active management of dietary Phe intake using medical foods and natural sources of proteins is required to ensure blood Phe control and adequate nutritional balance.

What Are the Benefits of Taking Kuvan (saproterin dihydrochloride tablets) ?

Prolonged high blood Phe levels are neurotoxic and lead to impairment of intelligence and other brain functions (such as attentiveness). Reduction of blood Phe levels through dietary control is an important determinant of long-term neurologic outcome in PKU patients, and reduction of blood Phe levels in patients with PKU has been shown to decrease the long-term risk of neurologic injury. It is difficult for many patients to maintain reduced blood Phe, and many patients with PKU experience some degree of neurological impairment despite efforts to maintain dietary Phe control.

In clinical trials with Kuvan (saproterin dihydrochloride tablets) in patients with PKU, reductions in blood Phe levels were observed in some patients. Although long-term assessment of neurologic function in patients with PKU receiving Kuvan (saproterin dihydrochloride tablets) for the treatment of elevated blood Phe has not been assessed, Kuvan (saproterin dihydrochloride tablets) may help maintain reduced blood Phe levels as an adjunct to a Phe-controlled diet.

What Are the Risks of Taking Kuvan (saproterin dihydrochloride tablets) ?

Response to Kuvan (saproterin dihydrochloride tablets) treatment in PKU patients is variable. Not all patients responded to treatment with Kuvan (saproterin dihydrochloride tablets) in clinical trials, and the initiation of Kuvan (saproterin dihydrochloride tablets) treatment does not eliminate the need to monitor for adequate blood Phe control. Prolonged elevations in blood Phe levels can result in neurologic impairment. Conversely, some patients in clinical trials who were following Phe-restricted diets and received treatment with Kuvan (saproterin dihydrochloride tablets) experienced substantial reductions of blood Phe. Levels of blood Phe that are too low may be associated with catabolism and protein breakdown. Therefore, when Kuvan (saproterin dihydrochloride tablets) is used in combination with a Phe-restricted diet, patients should be monitored closely to ensure that blood Phe levels are not too low, and, if necessary, the dose of Kuvan (saproterin dihydrochloride tablets) should be adjusted.

The most serious adverse reactions during Kuvan (saproterin dihydrochloride tablets) administration (regardless of relationship to treatment) were gastritis, spinal cord injury, streptococcal infection, testicular carcinoma, and urinary tract infection. Mild to moderate neutropenia was noted during Kuvan (saproterin dihydrochloride tablets) administration in 24 of 579 patients (4%). The most common ( ≥ 4% of patients treated with Kuvan (saproterin dihydrochloride tablets) ) across all studies (n=579) were headache, diarrhea, abdominal pain, upper respiratory tract infection, pharyngolaryngeal pain, vomiting, and nausea [see ADVERSE REACTIONS].

Long-term studies of neurocognitive outcomes have not been conducted with Kuvan (saproterin dihydrochloride tablets) .

BioMarin PKU Disease Registries

BioMarin will establish a general disease registry for PKU patients and a pregnancy registry for women who are pregnant while receiving Kuvan (saproterin dihydrochloride tablets) treatment.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

A 2-year carcinogenicity study was conducted in F-344 rats, and a 78-week carcinogenicity study was conducted in CD-1 mice. In the 104-week oral carcinogenicity study in rats, sapropterin doses of 25, 80, and 250 mg/kg/day (0.2, 0.7, and 2 times the maximum recommended human dose of 20 mg/kg/day, respectively, based on body surface area) were used. In the 78-week oral carcinogenicity study in mice, sapropterin doses of 25, 80, and 250 mg/kg/day (0.1, 0.3, and 2 times the recommended human dose, respectively, based on body surface area) were used. In the 2-year rat carcinogenicity study, there was a statistically significant increase in the incidence of benign adrenal pheochromocytoma in male rats treated with the 250 mg/kg/day (about 2 times the maximum recommended human dose, based on body surface area) dose, as compared to vehicle-treated rats. The mouse carcinogenicity study showed no evidence of a carcinogenic effect, but the study was not ideal due to its duration of 78 instead of 104 weeks.

Sapropterin was genotoxic in thein vitroAmes test at concentrations of 625 µg (TA98) and 5000 µg (TA100) per plate, without metabolic activation. However, no genotoxicity was observed in the in vitro Ames test with metabolic activation. Sapropterin was genotoxic in the in vitro chromosomal aberration assay in Chinese hamster lung cells at concentrations of 0.25 and 0.5 mM. Sapropterin was not mutagenic in the in vivo micronucleus assay in mice at doses up to 2000 mg/kg/day (about 8 times the maximum recommended human dose of 20 mg/kg/day, based on body surface area). Sapropterin, at oral doses up to 400 mg/kg/day (about 3 times the maximum recommended human dose, based on body surface area) was found to have no effect on fertility and reproductive function of male and female rats.

Use In Specific Populations

Pregnancy

Pregnancy Category C. Women who are exposed to Kuvan (saproterin dihydrochloride tablets) during pregnancy are encouraged to enroll in the Kuvan (saproterin dihydrochloride tablets) patient registry [see Patient Counseling Information].

Teratogenicity studies with sapropterin have been conducted in rats at oral doses up to 400 mg/kg/day (about 3 times the maximum recommended human dose of 20 mg/kg/day, based on body surface area) and in rabbits at oral doses of up to 600 mg/kg/day (about 10 times the maximum recommended human dose, based on body surface area). No clear evidence of teratogenic activity was found in either species; however, in the rabbit teratogenicity study, there was an increase (not statistically significant) in the incidence of holoprosencephaly at the 600 mg/kg/day dose compared to controls.

There are no adequate and well-controlled studies of Kuvan (saproterin dihydrochloride tablets) in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed. A study of 468 pregnancies and 331 live births in PKU-affected women (Maternal Phenylketonuria Collaborative Study, Rouse 1997) has demonstrated that uncontrolled Phe levels above 600 µmol/L are associated with a very high incidence of neurological, cardiac, facial dysmorphism, and growth anomalies. Good dietary control of Phe levels during pregnancy is essential in reducing the incidence of Phe-induced teratogenic effects.

Labor and Delivery

The effects of Kuvan (saproterin dihydrochloride tablets) on labor and delivery in pregnant women are unknown.

Nursing Mothers

Sapropterin is excreted in the milk of intravenously, but not orally treated lactating rats. It is not known whether sapropterin is excreted in human milk. Because of the potential for serious adverse reactions in nursing infants from sapropterin and because of the potential for tumorigenicity shown for sapropterin in the rat carcinogenicity study, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use

Pediatric patients with PKU, ages 4 to 16 years, have been treated with Kuvan in clinical studies [see Clinical Studies]. The safety and efficacy of Kuvan (saproterin dihydrochloride tablets) in pediatric patients less than 4 years of age have not been assessed in clinical studies. Frequent blood monitoring is recommended in the pediatric population to ensure adequate blood Phe level control [see Patient Counseling Information].

Geriatric Use

Clinical studies of Kuvan (saproterin dihydrochloride tablets) in patients with PKU did not include patients aged 65 years and older. It is not known whether these patients respond differently than younger patients.

Patients With Renal Impairment

Patients with renal impairment have not been evaluated in clinical trials. Patients who have renal impairment should be carefully monitored when receiving Kuvan (saproterin dihydrochloride tablets) .

Last reviewed on RxList: 1/3/2008
This monograph has been modified to include the generic and brand name in many instances.

OVERDOSE

In the only reported overdosage with Kuvan (saproterin dihydrochloride tablets) , a patient participating in a 26-week study received a single dose of 4,500 mg (36 mg/kg) instead of 2,600 mg (20 mg/kg) in Week 16. The patient reported mild headache and mild dizziness immediately after taking the dose; both symptoms resolved within 1 hour with no treatment intervention. Results from liver function laboratory tests obtained immediately following the event were within normal limits. The patient suspended therapy for 24 hours and then restarted Kuvan (saproterin dihydrochloride tablets) with no reports of abnormal signs or symptoms.

CONTRAINDICATIONS

None.

Last reviewed on RxList: 1/3/2008
This monograph has been modified to include the generic and brand name in many instances.

CLINICAL PHARMACOLOGY

Mechanism of Action

Kuvan (saproterin dihydrochloride tablets) is a synthetic form of BH4, the cofactor for the enzyme phenylalanine hydroxylase (PAH). PAH hydroxylates Phe through an oxidative reaction to form tyrosine. In patients with PKU, PAH activity is absent or deficient. Treatment with BH4 can activate residual PAH enzyme, improve the normal oxidative metabolism of Phe, and decrease Phe levels in some patients.

Pharmacodynamics

In PKU patients who are responsive to BH4 treatment, blood Phe levels decrease within 24 hours after a single administration of sapropterin dihydrochloride, although maximal effect on Phe level may take up to a month, depending on the patient. A single daily dose of Kuvan (saproterin dihydrochloride tablets) is adequate to maintain stable blood Phe levels over a 24-hour period. Twelve patients with blood Phe levels ranging from 516 to 986 µmol/L (mean 747 ± 153 µmol/L) were assessed with 24-hour blood Phe level monitoring following a daily morning dose of 10 mg/kg/day. The blood Phe level remained stable during a 24-hour observation period. No substantial increases in blood Phe levels were observed following food intake throughout the 24-hour period.

Doses above 20 mg/kg/day have not been evaluated in clinical studies.

Pharmacokinetics

Studies in healthy volunteers have shown comparable absorption of sapropterin dihydrochloride when tablets are dissolved in water or orange juice and taken under fasted conditions. Administration of dissolved tablets after a high-fat/high-calorie meal resulted in mean increases in Cmax of 84% and AUC of 87% (dissolved in water). However, there was extensive variability in individual subject values for Cmax and AUC across the different modes of administration and meal conditions. In the clinical trials of Kuvan (saproterin dihydrochloride tablets) , drug was administered in the morning as a dissolved tablet without regard to meals. The mean elimination half-life in PKU patients was approximately 6.7 hours (range 3.9 to 17 hr), comparable with values seen in healthy subjects (range 3.0 to 5.3 hr).

A population pharmacokinetic analysis of sapropterin that included patients between 9 and 49 years of age showed no effect of age on sapropterin dihydrochloride pharmacokinetics. Pharmacokinetics in patients < 9 years and > 49 years of age have not been studied.

Clinical Studies

Clinical Studies in PKU

The efficacy and safety of Kuvan (saproterin dihydrochloride tablets) were evaluated in 4 clinical studies in patients with PKU.

Study 1 was a multicenter, open-label, uncontrolled clinical trial of 489 patients with PKU, ages 8 to 48 years (mean 22 years), who had baseline blood Phe levels ≥ 450 µmol/L and who were not on Phe-restricted diets. All patients received treatment with Kuvan (saproterin dihydrochloride tablets) 10 mg/kg/day for 8 days. For the purposes of this study, response to Kuvan (saproterin dihydrochloride tablets) treatment was defined as a ≥ 30% decrease in blood Phe from baseline. At Day 8, 96 patients (20%) were identified as responders.

Study 2 was a multicenter, double-blind, placebo-controlled study of 88 patients with PKU who responded to Kuvan (saproterin dihydrochloride tablets) in Study 1. After a washout period from Study 1, patients were randomized equally to either Kuvan (saproterin dihydrochloride tablets) 10 mg/kg/day (N=41) or placebo (N=47) for 6 weeks. Efficacy was assessed by the mean change in blood Phe level from baseline to Week 6 in the Kuvan (saproterin dihydrochloride tablets) -treated group as compared to the mean change in the placebo group.

The results showed that at baseline, the mean (±SD) blood Phe level was 843 (±300) µmol/L in the Kuvan (saproterin dihydrochloride tablets) -treated group and 888 (±323) µmol/L in the placebo group. At Week 6, the Kuvan (saproterin dihydrochloride tablets) -treated group had a mean (±SD) blood Phe level of 607 (±377) µmol/L, and the placebo group had a mean blood Phe level of 891 (±348) µmol/L. At Week 6, the Kuvan (saproterin dihydrochloride tablets) - and placebo-treated groups had mean changes in blood Phe level of -239 and 6 µmol/L, respectively (mean percent changes of -29% (±32) and 3% (±33), respectively). The difference between the groups was statistically significant (p < 0.001) (Table 2).

Table 2: Blood Phe Results in Study 2


  Sapropterin
(N=41)
Placebo
(N=47)
Baseline Blood Phe Level1 (µmol/L)
  Mean (±SD) 843 (±300) 888 (±323)
  Percentiles (25th, 75th) 620, 990 618, 1141
Week 6 Blood Phe Level (µmol/L)
  Mean (±SD) 607 (±377) 891 (±348)
  Percentiles (25th, 75th) 307, 812 619, 1143
Mean Change in Blood Phe From Baseline to Week 6 (µmol/L)
  Adjusted Mean (±SE)2 -239 (±38) 6 (±36)
  Percentiles (25th, 75th) -397, -92 -96, 93
Mean Percent Change in Blood Phe From Baseline to Week 6
  Mean (±SD) - 29 (±32) 3 (±33)
  Percentiles (25th, 75th) -61, -11 -13, 12
1The mean baseline (BL) levels shown in this table represent the mean of 3 pretreatment levels (Wk -2, Wk -1, and Wk 0). Treatment with Kuvan (saproterin dihydrochloride tablets) or placebo started at Wk 0.
2p-value < 0.001, adjusted mean and standard error from an ANCOVA model with change in blood Phe level from baseline to Week 6 as the response variable, and both treatment group and baseline blood Phe level as covariates.

Change in blood Phe was noted in the Kuvan (saproterin dihydrochloride tablets) -treated group at Week 1 and was sustained through Week 6 (Figure 1).

Figure 1: Mean Blood Phenylalanine (Phe) Level Over Time1


Mean Blood Phenylalanine (Phe) Level Over Time - illustration

Study 3 was a multicenter, open-label, extension study in which 80 patients who responded to Kuvan (saproterin dihydrochloride tablets) treatment in Study 1 and completed Study 2 underwent 6 weeks of forced dose-titration with 3 different doses of Kuvan (saproterin dihydrochloride tablets) . Treatments consisted of 3 consecutive 2-week courses of Kuvan (saproterin dihydrochloride tablets) at doses of 5, then 20, and then 10 mg/kg/day. Blood Phe level was monitored after 2 weeks of treatment at each dose level. At baseline, mean (±SD) blood Phe was 844 (±398) µmol/L. At the end of treatment with 5, 10, and 20 mg/kg/day, mean (±SD) blood Phe levels were 744 (±384) µmol/L, 640 (±382) µmol/L, and 581 (±399) µmol/L, respectively (Table 3).

Table 3: Blood Phe Results From Forced Dose-Titration in Study 3


Kuvan Dose Level
(mg/kg/day)
No. of
Patients
Mean (±SD) Blood
Phe Level (µmol/L)
Mean Changes (±SD) in
Blood Phe Level From
Week 0 (µmol/L)
Baseline
(No Treatment)
80 844 (±398) -
5 80 744 (±384) -100 (±295)
10 80 640 (±382) -204 (±303)
20 80 581 (±399) -263 (±318)

Study 4 was a multicenter study of 90 children with PKU, ages 4 to 12 years, who were on Phe-restricted diets and who had blood Phe levels ≤ 480 µmol/L at screening. All patients were treated with open-label Kuvan (saproterin dihydrochloride tablets) 20 mg/kg/day for 8 days. Response to Kuvan (saproterin dihydrochloride tablets) was defined as a ≥ 30% decrease in blood Phe from baseline at Day 8. At Day 8, 50 patients (56%) had a ≥ 30% decrease in blood Phe.

Last reviewed on RxList: 1/3/2008
This monograph has been modified to include the generic and brand name in many instances.

PATIENT INFORMATION

Kuvan (COO-van)
(sapropterin dihydrochloride) Tablets

For people with PKU

Read this leaflet before you start taking Kuvan (saproterin dihydrochloride tablets) and each time you get a refill. There may be new information. This information does not take the place of talking with your doctor about your medical condition or treatment.

What is Kuvan (saproterin dihydrochloride tablets) ?

Kuvan (saproterin dihydrochloride tablets) is a medicine for people with Phenylketonuria (PKU). An enzyme in your body PAH (phenylalanine hydroxylase) helps break down phenylalanine (Phe), an amino acid found in food. In patients with PKU this enzyme does not work right. PKU leads to high blood Phe levels. High blood Phe levels are toxic to the brain and can lead to lower intelligence and decrease in the ability to focus, remember, and organize information.

How does Kuvan (saproterin dihydrochloride tablets) work?

Kuvan (saproterin dihydrochloride tablets) acts in your body with the enzyme PAH to reduce your blood Phe levels. Your doctor and health care team will continue to monitor your blood Phe levels and dietary Phe intake.

Kuvan (saproterin dihydrochloride tablets) are tablets that you should dissolve in water or apple juice before taking.

Who may benefit from taking Kuvan (saproterin dihydrochloride tablets) ?

It is not possible to know whether or not Kuvan (saproterin dihydrochloride tablets) will work for you until you start taking Kuvan (saproterin dihydrochloride tablets) . Your doctor will monitor your blood Phe levels when you start taking Kuvan (saproterin dihydrochloride tablets) to see if the drug is working.

What are the risks of taking Kuvan (saproterin dihydrochloride tablets) ?

When you are taking Kuvan (saproterin dihydrochloride tablets) , any change you make to your diet may affect your blood Phe level. Follow your doctor's instructions carefully and do not make any changes to your dietary Phe intake before discussing with your doctor. Your doctor will continue to monitor your blood Phe levels during your treatment with Kuvan (saproterin dihydrochloride tablets) .

If you have a fever, or if you are sick, your blood Phe level may go up. Tell your doctor as soon as possible so they can see if they have to adjust your treatment to help keep your blood Phe levels in the desired range.

What should I tell my doctor before taking Kuvan (saproterin dihydrochloride tablets) ?

Before you start taking Kuvan (saproterin dihydrochloride tablets) , let your doctor know about all of your medical conditions, including if you:

  • Have a fever
  • Are pregnant or planning to become pregnant
  • Are breast feeding
  • Have liver problems
  • Are allergic to Kuvan (saproterin dihydrochloride tablets) or any other medications
  • Have poor nutrition or are anorexic
  • Are taking levodopa
  • Are taking drugs that inhibit folate metabolism (e.g., methotrexate) because these drugs could affect how Kuvan (saproterin dihydrochloride tablets) works in your body
  • Are taking medicines for erectile dysfunction like Viagra (sildenafil), Levitra (vardenafil), or Cialis (tadalafil)

Tell your doctor about all the medicines you take, including prescription and nonprescription medicines and herbal and dietary supplements. Kuvan (saproterin dihydrochloride tablets) and many other medicines may interact with each other. Your doctor needs to know what medicines you take so he or she can decide if Kuvan (saproterin dihydrochloride tablets) is right for you.

Know the medicines you take. Keep a list of your medicines with you to show your doctor. Do not take other medicines while taking Kuvan (saproterin dihydrochloride tablets) without first talking to your doctor.

How should I take Kuvan (saproterin dihydrochloride tablets) ?

Kuvan (saproterin dihydrochloride tablets) Tablets are taken at one time each day. Take Kuvan (saproterin dihydrochloride tablets) exactly as your doctor has told you.

  • Take Kuvan (saproterin dihydrochloride tablets) once a day with food and preferably at the same time each day.
  • Kuvan (saproterin dihydrochloride tablets) Tablets should be dissolved in 4 to 8 ounces (1/2 to 1 cup) of water or apple juice.
  • To dissolve the tablets, mix them in water or apple juice, and drink within 15 minutes.
    • It may take a few minutes for the tablets to dissolve. To make the tablets dissolve faster, you can stir or crush them.
    • The tablets may not dissolve completely. You may see small pieces floating on top of the water or apple juice. This is normal and safe for you to swallow.
    • If after drinking your medicine you still see small pieces of the tablet, you should add more water or apple juice to make sure that you take all of your medicine.
  • If you forget to take your dose of Kuvan (saproterin dihydrochloride tablets) , take it as soon as you remember that day. If you miss a day, do not double your dose the next day, just skip the missed dose.
  • The recommended starting dose of Kuvan (saproterin dihydrochloride tablets) is 10 mg/kg taken once a day. Your doctor will tell you the dose you should take and when to take it.
  • Your doctor can change your dose depending on how you respond to treatment.

What are the possible side effects of Kuvan (saproterin dihydrochloride tablets) ?

The most common side effects reported when using Kuvan (saproterin dihydrochloride tablets) are:

  • Headache
  • Diarrhea
  • Abdominal pain
  • Upper respiratory tract infection (like a cold)
  • Throat pain
  • Vomiting
  • Nausea

These are not all the side effects seen with Kuvan (saproterin dihydrochloride tablets) . If you are concerned about these or any other side effects you experience while taking Kuvan (saproterin dihydrochloride tablets) , ask your doctor or pharmacist for more information.

Be sure to tell your doctor if you have any side effects when you are taking Kuvan (saproterin dihydrochloride tablets) .

How should I store Kuvan (saproterin dihydrochloride tablets) ?

  • Store in a cool, dry place between 68°F and 77°F (20-25°C).
  • Do not leave Kuvan (saproterin dihydrochloride tablets) in hot or humid places, such as your car or bathroom cabinet.
  • Keep Kuvan (saproterin dihydrochloride tablets) in its original bottle with the cap closed tightly.
  • Protect from moisture. Do not remove the dessicant (the small packet included with your tablets). The dessicant absorbs moisture.
  • The color of the tablets may change over time to light yellow. This is normal and you can take these tablets.
  • Do not keep Kuvan (saproterin dihydrochloride tablets) that is out of date, or that you no longer need. Be sure that if you throw any medicine away, it is out of the reach of children.
  • Keep Kuvan (saproterin dihydrochloride tablets) and all medicines out of the reach of children.

General information about Kuvan (saproterin dihydrochloride tablets)

Medicines are sometimes prescribed for conditions that are not mentioned in patient information leaflets. Do not use Kuvan (saproterin dihydrochloride tablets) for any other condition. Do not give Kuvan (saproterin dihydrochloride tablets) to anyone else, even if they have the same condition that you have. It may harm them.

This leaflet summarizes the most important information about Kuvan (saproterin dihydrochloride tablets) . If you would like more information, talk with your doctor. You can ask your doctor or pharmacist for information about Kuvan (saproterin dihydrochloride tablets) that is written for health professionals. For more information you can call BioMarin Patient and Physician Support (BPPS) for free at 1-866-906-6100.

What are the ingredients in Kuvan?

Active Ingredient: sapropterin dihydrochloride.

Inactive Ingredients: ascorbic acid, crospovidone, dibasic calcium phosphate, D-mannitol, riboflavin, and sodium stearyl fumarate.

Kuvan (saproterin dihydrochloride tablets) Tablets are mottled, off-white to light yellow, and debossed with "177".

Last reviewed on RxList: 1/3/2008
This monograph has been modified to include the generic and brand name in many instances.

>

PATIENT INFORMATION

Kuvan (COO-van)
(sapropterin dihydrochloride) Tablets

For people with PKU

Read this leaflet before you start taking Kuvan (saproterin dihydrochloride tablets) and each time you get a refill. There may be new information. This information does not take the place of talking with your doctor about your medical condition or treatment.

What is Kuvan (saproterin dihydrochloride tablets) ?

Kuvan (saproterin dihydrochloride tablets) is a medicine for people with Phenylketonuria (PKU). An enzyme in your body PAH (phenylalanine hydroxylase) helps break down phenylalanine (Phe), an amino acid found in food. In patients with PKU this enzyme does not work right. PKU leads to high blood Phe levels. High blood Phe levels are toxic to the brain and can lead to lower intelligence and decrease in the ability to focus, remember, and organize information.

How does Kuvan (saproterin dihydrochloride tablets) work?

Kuvan (saproterin dihydrochloride tablets) acts in your body with the enzyme PAH to reduce your blood Phe levels. Your doctor and health care team will continue to monitor your blood Phe levels and dietary Phe intake.

Kuvan (saproterin dihydrochloride tablets) are tablets that you should dissolve in water or apple juice before taking.

Who may benefit from taking Kuvan (saproterin dihydrochloride tablets) ?

It is not possible to know whether or not Kuvan (saproterin dihydrochloride tablets) will work for you until you start taking Kuvan (saproterin dihydrochloride tablets) . Your doctor will monitor your blood Phe levels when you start taking Kuvan (saproterin dihydrochloride tablets) to see if the drug is working.

What are the risks of taking Kuvan (saproterin dihydrochloride tablets) ?

When you are taking Kuvan (saproterin dihydrochloride tablets) , any change you make to your diet may affect your blood Phe level. Follow your doctor's instructions carefully and do not make any changes to your dietary Phe intake before discussing with your doctor. Your doctor will continue to monitor your blood Phe levels during your treatment with Kuvan (saproterin dihydrochloride tablets) .

If you have a fever, or if you are sick, your blood Phe level may go up. Tell your doctor as soon as possible so they can see if they have to adjust your treatment to help keep your blood Phe levels in the desired range.

What should I tell my doctor before taking Kuvan (saproterin dihydrochloride tablets) ?

Before you start taking Kuvan (saproterin dihydrochloride tablets) , let your doctor know about all of your medical conditions, including if you:

  • Have a fever
  • Are pregnant or planning to become pregnant
  • Are breast feeding
  • Have liver problems
  • Are allergic to Kuvan (saproterin dihydrochloride tablets) or any other medications
  • Have poor nutrition or are anorexic
  • Are taking levodopa
  • Are taking drugs that inhibit folate metabolism (e.g., methotrexate) because these drugs could affect how Kuvan (saproterin dihydrochloride tablets) works in your body
  • Are taking medicines for erectile dysfunction like Viagra (sildenafil), Levitra (vardenafil), or Cialis (tadalafil)

Tell your doctor about all the medicines you take, including prescription and nonprescription medicines and herbal and dietary supplements. Kuvan (saproterin dihydrochloride tablets) and many other medicines may interact with each other. Your doctor needs to know what medicines you take so he or she can decide if Kuvan (saproterin dihydrochloride tablets) is right for you.

Know the medicines you take. Keep a list of your medicines with you to show your doctor. Do not take other medicines while taking Kuvan (saproterin dihydrochloride tablets) without first talking to your doctor.

How should I take Kuvan (saproterin dihydrochloride tablets) ?

Kuvan (saproterin dihydrochloride tablets) Tablets are taken at one time each day. Take Kuvan (saproterin dihydrochloride tablets) exactly as your doctor has told you.

  • Take Kuvan (saproterin dihydrochloride tablets) once a day with food and preferably at the same time each day.
  • Kuvan (saproterin dihydrochloride tablets) Tablets should be dissolved in 4 to 8 ounces (1/2 to 1 cup) of water or apple juice.
  • To dissolve the tablets, mix them in water or apple juice, and drink within 15 minutes.
    • It may take a few minutes for the tablets to dissolve. To make the tablets dissolve faster, you can stir or crush them.
    • The tablets may not dissolve completely. You may see small pieces floating on top of the water or apple juice. This is normal and safe for you to swallow.
    • If after drinking your medicine you still see small pieces of the tablet, you should add more water or apple juice to make sure that you take all of your medicine.
  • If you forget to take your dose of Kuvan (saproterin dihydrochloride tablets) , take it as soon as you remember that day. If you miss a day, do not double your dose the next day, just skip the missed dose.
  • The recommended starting dose of Kuvan (saproterin dihydrochloride tablets) is 10 mg/kg taken once a day. Your doctor will tell you the dose you should take and when to take it.
  • Your doctor can change your dose depending on how you respond to treatment.

What are the possible side effects of Kuvan (saproterin dihydrochloride tablets) ?

The most common side effects reported when using Kuvan (saproterin dihydrochloride tablets) are:

  • Headache
  • Diarrhea
  • Abdominal pain
  • Upper respiratory tract infection (like a cold)
  • Throat pain
  • Vomiting
  • Nausea

These are not all the side effects seen with Kuvan (saproterin dihydrochloride tablets) . If you are concerned about these or any other side effects you experience while taking Kuvan (saproterin dihydrochloride tablets) , ask your doctor or pharmacist for more information.

Be sure to tell your doctor if you have any side effects when you are taking Kuvan (saproterin dihydrochloride tablets) .

How should I store Kuvan (saproterin dihydrochloride tablets) ?

  • Store in a cool, dry place between 68°F and 77°F (20-25°C).
  • Do not leave Kuvan (saproterin dihydrochloride tablets) in hot or humid places, such as your car or bathroom cabinet.
  • Keep Kuvan (saproterin dihydrochloride tablets) in its original bottle with the cap closed tightly.
  • Protect from moisture. Do not remove the dessicant (the small packet included with your tablets). The dessicant absorbs moisture.
  • The color of the tablets may change over time to light yellow. This is normal and you can take these tablets.
  • Do not keep Kuvan (saproterin dihydrochloride tablets) that is out of date, or that you no longer need. Be sure that if you throw any medicine away, it is out of the reach of children.
  • Keep Kuvan (saproterin dihydrochloride tablets) and all medicines out of the reach of children.

General information about Kuvan (saproterin dihydrochloride tablets)

Medicines are sometimes prescribed for conditions that are not mentioned in patient information leaflets. Do not use Kuvan (saproterin dihydrochloride tablets) for any other condition. Do not give Kuvan (saproterin dihydrochloride tablets) to anyone else, even if they have the same condition that you have. It may harm them.

This leaflet summarizes the most important information about Kuvan (saproterin dihydrochloride tablets) . If you would like more information, talk with your doctor. You can ask your doctor or pharmacist for information about Kuvan (saproterin dihydrochloride tablets) that is written for health professionals. For more information you can call BioMarin Patient and Physician Support (BPPS) for free at 1-866-906-6100.

What are the ingredients in Kuvan?

Active Ingredient: sapropterin dihydrochloride.

Inactive Ingredients: ascorbic acid, crospovidone, dibasic calcium phosphate, D-mannitol, riboflavin, and sodium stearyl fumarate.

Kuvan (saproterin dihydrochloride tablets) Tablets are mottled, off-white to light yellow, and debossed with "177".

Last reviewed on RxList: 1/3/2008
This monograph has been modified to include the generic and brand name in many instances.

Kuvan
(sapropterin dihydrochloride) Tablets

DRUG DESCRIPTION

Sapropterin dihydrochloride, the active pharmaceutical ingredient in Kuvan (saproterin dihydrochloride tablets) Tablets, is a synthetic preparation of the dihydrochloride salt of naturally occurring tetrahydrobiopterin (BH4). Sapropterin dihydrochloride is an off-white to light yellow crystals or crystalline powder.

The chemical name of sapropterin dihydrochloride is (6R)-2-amino-6-[(1R,2S)-1,2- dihydroxypropyl]-5,6,7,8-tetrahydro-4(1H)-pteridinone dihydrochloride and the molecular formula is C9H15N5O3·2HCl with a molecular weight of 314.17.

Sapropterin dihydrochloride has the following structural formula:

Kuvan (sapropterin dihydrochloride) structural formula illustration

Each Kuvan Tablet contains 100 mg of sapropterin dihydrochloride (equivalent to 76.8 mg of sapropterin base). Tablets are round, off-white to light yellow, mottled, and debossed with “177”. Each tablet contains the following inactive ingredients: ascorbic acid (USP), crospovidone (NF), dibasic calcium phosphate (USP), D-mannitol (USP), riboflavin (USP), and sodium stearyl fumarate (NF).

Last reviewed on RxList: 1/3/2008
This monograph has been modified to include the generic and brand name in many instances.

Kuvan
(sapropterin dihydrochloride) Tablets

DRUG DESCRIPTION

Sapropterin dihydrochloride, the active pharmaceutical ingredient in Kuvan (saproterin dihydrochloride tablets) Tablets, is a synthetic preparation of the dihydrochloride salt of naturally occurring tetrahydrobiopterin (BH4). Sapropterin dihydrochloride is an off-white to light yellow crystals or crystalline powder.

The chemical name of sapropterin dihydrochloride is (6R)-2-amino-6-[(1R,2S)-1,2- dihydroxypropyl]-5,6,7,8-tetrahydro-4(1H)-pteridinone dihydrochloride and the molecular formula is C9H15N5O3·2HCl with a molecular weight of 314.17.

Sapropterin dihydrochloride has the following structural formula:

Kuvan (sapropterin dihydrochloride) structural formula illustration

Each Kuvan Tablet contains 100 mg of sapropterin dihydrochloride (equivalent to 76.8 mg of sapropterin base). Tablets are round, off-white to light yellow, mottled, and debossed with “177”. Each tablet contains the following inactive ingredients: ascorbic acid (USP), crospovidone (NF), dibasic calcium phosphate (USP), D-mannitol (USP), riboflavin (USP), and sodium stearyl fumarate (NF).

Last reviewed on RxList: 1/3/2008
This monograph has been modified to include the generic and brand name in many instances.

Kuvan
(sapropterin dihydrochloride) Tablets

DRUG DESCRIPTION

Sapropterin dihydrochloride, the active pharmaceutical ingredient in Kuvan (saproterin dihydrochloride tablets) Tablets, is a synthetic preparation of the dihydrochloride salt of naturally occurring tetrahydrobiopterin (BH4). Sapropterin dihydrochloride is an off-white to light yellow crystals or crystalline powder.

The chemical name of sapropterin dihydrochloride is (6R)-2-amino-6-[(1R,2S)-1,2- dihydroxypropyl]-5,6,7,8-tetrahydro-4(1H)-pteridinone dihydrochloride and the molecular formula is C9H15N5O3·2HCl with a molecular weight of 314.17.

Sapropterin dihydrochloride has the following structural formula:

Kuvan (sapropterin dihydrochloride) structural formula illustration

Each Kuvan Tablet contains 100 mg of sapropterin dihydrochloride (equivalent to 76.8 mg of sapropterin base). Tablets are round, off-white to light yellow, mottled, and debossed with “177”. Each tablet contains the following inactive ingredients: ascorbic acid (USP), crospovidone (NF), dibasic calcium phosphate (USP), D-mannitol (USP), riboflavin (USP), and sodium stearyl fumarate (NF).

Last reviewed on RxList: 1/3/2008
This monograph has been modified to include the generic and brand name in many instances.

Kuvan Patient Information Including Side Effects

Brand Names: Kuvan

Generic Name: sapropterin (Pronunciation: SAP roe TER in)

What is sapropterin (Kuvan)?

Sapropterin is a synthetic form of a natural salt that contributes to the function of a certain enzyme in the body. In people with a condition called phenylketonuria (PKU), this enzyme is lacking or missing in the body. Without the enzyme, phenylalanine levels can become elevated and cause a variety of neurologic symptoms.

Sapropterin is used to help the body activate the enzyme needed to control blood levels of phenylalanine. This medication is used in people with PKU.

Sapropterin may also be used for other purposes not listed in this medication guide.

What are the possible side effects of sapropterin (Kuvan)?

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 Kuvan (saproterin dihydrochloride tablets) Side Effects Center for a complete guide to possible side effects »

What is the most important information I should know about sapropterin (Kuvan)?

Before using sapropterin, tell your doctor if you are allergic to any drugs, or if you have liver disease, a history of stomach ulcer or bleeding, or a seizure disorder.

Also tell your doctor about any medications you use, especially levodopa (Larodopa, Altamet, Parcopa, Sinemet), methotrexate (Rheumatrex, Trexall), or any medication to treat erectile dysfunction, such as sildenafil (Viagra), tadalafil (Cialis), or vardenafil (Levitra).

To be sure sapropterin is helping your condition, your blood will need to be tested on a regular basis. Do not miss any scheduled appointments.

Sapropterin is only part of a complete program of treatment that also includes a special diet. It is very important to follow the diet plan created for you by your doctor or nutrition counselor. You should become very familiar with the list of foods you must avoid to help control your condition.

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 if you have any of these symptoms.

Follow your doctor's instructions about any restrictions on food, beverages, or activity while you are using sapropterin.

Side Effects Centers

Kuvan Patient Information including How Should I Take

What should I discuss with my health care provider before taking sapropterin (Kuvan)?

Before using sapropterin, tell your doctor if you are allergic to any drugs, or if you have:

  • liver disease;
  • a history of stomach ulcer or bleeding; or
  • epilepsy or other seizure disorder.

If you have any of these conditions, you may not be able to take sapropterin, or you may need a dose adjustment or special tests during treatment.

FDA pregnancy category C. This medication may be harmful to an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant during treatment.

It is not known whether sapropterin passes into breast milk or if it could harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

How should I take sapropterin (Kuvan)?

Take this medication exactly as prescribed by your doctor. Do not take it in larger amounts or for longer than recommended. Follow the directions on your prescription label.

Sapropterin is usually given once daily. Follow your doctor's instructions.

Sapropterin works best if you take it with food.

Dissolve the tablet in 4 to 8 ounces of water or apple juice. It will take about 15 minutes for the tablet to dissolve. Stir this mixture and then drink all of it right away. To make sure you get the entire dose, add a little more water or juice to the same glass, swirl gently and drink right away.

The tablet may not completely dissolve and you may see small pieces in the liquid. These pieces are safe for you to swallow.

To be sure this medication is helping your condition, your blood will need to be tested on a regular basis. Do not miss any scheduled appointments.

Sapropterin can reduce your phenylalanine blood levels within 24 hours of when you take it. However, it may take up to 30 days of using this medicine before it reaches its fullest effect in your body. For best results, keep using the medication as directed.

Sapropterin is only part of a complete program of treatment that also includes a special diet. It is very important to follow the diet plan created for you by your doctor or nutrition counselor. You should become very familiar with the list of foods you must avoid to help control your condition.

Store sapropterin at room temperature away from moisture and heat. Keep the bottle tightly closed when not in use.

Side Effects Centers

Kuvan Patient Information including If I Miss a Dose

What happens if I miss a dose (Kuvan)?

Take the missed dose as soon as you remember. If it is almost time for your next dose, wait until then to take the medicine and skip the missed dose. Do not take extra medicine to make up the missed dose.

Do not take 2 doses on the same day.

What happens if I overdose (Kuvan)?

Seek emergency medical attention if you think you have used too much of this medicine.

Overdose symptoms may include headache and dizziness.

What should I avoid while taking sapropterin (Kuvan)?

Follow your doctor's instructions about any restrictions on food, beverages, or activity while you are using sapropterin.

What other drugs will affect sapropterin (Kuvan)?

The following drugs can interact with sapropterin. Tell your doctor if you are using any of these:

  • levodopa (Larodopa, Altamet, Parcopa, Sinemet);
  • methotrexate (Rheumatrex, Trexall);
  • sildenafil (Viagra);
  • tadalafil (Cialis); or
  • vardenafil (Levitra).

This list is not complete and there may be other drugs that can interact with sapropterin. Tell your doctor about all your prescription and over-the-counter medications, vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start a new medication without telling your doctor.

Where can I get more information?

Your pharmacist can provide more information about sapropterin.


Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

Every effort has been made to ensure that the information provided by Cerner Multum, Inc. ('Multum') is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. Multum information has been compiled for use by healthcare practitioners and consumers in the United States and therefore Multum does not warrant that uses outside of the United States are appropriate, unless specifically indicated otherwise. Multum's drug information does not endorse drugs, diagnose patients or recommend therapy. Multum's drug information is an informational resource designed to assist licensed healthcare practitioners in caring for their patients and/or to serve consumers viewing this service as a supplement to, and not a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient. Multum does not assume any responsibility for any aspect of healthcare administered with the aid of information Multum provides. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse or pharmacist.

Copyright 1996-2012 Cerner Multum, Inc. Version: 1.03. Revision date: 12/15/2010.

Your use of the content provided in this service indicates that you have read,understood and agree to the End-User License Agreement,which can be accessed by clicking on this link.

Healthwise

Side Effects Centers

توزیع کنندگان این دارو
شرکت های تولید کننده یا وارد کننده دارو

دارونـــما
نوآوری برای سلامت

طراحی و اجرا M.Ramezani
ارتباط با ما Info@darunama.com