FDA

Sapropterin Dihydrochloride

Approved 10 May 2019OralTablet

The FDA lists this product in 15 strengths and forms.

Indications

1. INDICATIONS AND USAGE Sapropterin dihydrochloride tablets are indicated to reduce blood phenylalanine (Phe) levels in adult and pediatric patients one month of age and older with hyperphenylalaninemia (HPA) due to tetrahydrobiopterin- (BH4-) responsive Phenylketonuria (PKU). Sapropterin dihydrochloride tablets are to be used in conjunction with a Phe-restricted diet. Sapropterin dihydrochloride tablets are a phenylalanine hydroxylase activator indicated to reduce blood phenylalanine (Phe) levels in adult and pediatric patients one month of age and older with hyperphenylalaninemia (HPA) due to tetrahydrobiopterin-(BH4-) responsive Phenylketonuria (PKU).

Sapropterin dihydrochloride tablets are to be used in conjunction with a Phe-restricted diet. (1)

Contraindications

4. CONTRAINDICATIONS None. None.

Warnings and precautions

5. WARNINGS AND PRECAUTIONS Hypersensitivity reactions including anaphylaxis : Sapropterin dihydrochloride tablets are not recommended in patients with a history of anaphylaxis to sapropterin dihydrochloride tablets; discontinue treatment in patients who experience anaphylaxis and initiate appropriate medical treatment. Continue dietary Phe restrictions. (5.1) Upper Gastrointestinal Mucosal Inflammation : Monitor patients for signs and symptoms of these conditions including esophagitis and gastritis.

(5.2) Hypophenylalaninemia : Pediatric patients younger than 7 years treated with Sapropterin dihydrochloride tablets doses of 20 mg/kg per day are at increased risk for low levels of blood Phe compared with patients 7 years and older. (5.3) Monitoring Blood Phe Levels During Treatment: Ensure adequate blood Phe control and nutritional balance during treatment with Sapropterin dihydrochloride tablets. Frequent blood monitoring is recommended, especially in pediatric patients.

(5.4, 2.1) Lack of Biochemical Response to Sapropterin Dihydrochloride Treatment : Response to sapropterin dihydrochloride treatment cannot be pre-determined by laboratory (e.g., molecular) testing and can only be determined by a therapeutic trial of sapropterin dihydrochloride. (5.5, 2.1) Interaction with Levodopa : Seizures, over-stimulation or irritability may occur; monitor patients for a change in neurologic status.

(5.6, 7) Hyperactivity : Monitor patients for hyperactivity. (5.7) 5.1. Hypersensitivity Reactions Including Anaphylaxis Sapropterin dihydrochloride is not recommended in patients with a history of anaphylaxis to sapropterin dihydrochloride. Hypersensitivity reactions, including anaphylaxis and rash, have occurred [see Adverse Reactions (6.2)]. Signs of anaphylaxis include wheezing, dyspnea, coughing, hypotension, flushing, nausea, and rash.

At a glance

Brand name: Sapropterin Dihydrochloride
Route: Oral
Dosage form: Tablet
Applicant: PH Health
Status: Prescription
FDA approval: 10 May 2019
Application: ANDA207200-001

Indications

Sapropterin dihydrochloride tablets are to be used in conjunction with a Phe-restricted diet. (1)

Warnings and precautions

Adverse reactions

6. ADVERSE REACTIONS Most common adverse reactions (≥4%) are: headache, rhinorrhea, pharyngolaryngeal pain, diarrhea, vomiting, cough, and nasal congestion. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Par Health at 1-800-828-9393, or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1. Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction 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 sapropterin dihydrochloride was evaluated in 7 clinical studies in patients with PKU (aged 1 month to 50 years) [see Clinical Studies (14)] . In Studies 1-4 (controlled and uncontrolled studies), 579 patients with PKU aged 4 to 49 years received sapropterin dihydrochloride 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 sapropterin dihydrochloride 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 sapropterin dihydrochloride in the double-blind, placebo-controlled clinical trials described above.

T able 3: Summary of Adverse Reactions Occurring in ≥4% of Patients in Placebo-Controlled Clinical Studies with Sapropterin dihydrochloride MedDRA Preferred Term Treatment Sapropterin dihydrochloride (N=74) Placebo(N=59) 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 sapropterin dihydrochloride in doses of 5 to 20 mg/kg per day, and adverse reactions were similar in type and frequency to those reported in the double-blind, placebo-controlled clinical trials [see Clinical Studies (14)] .

In Study 5, 65 pediatric patients with PKU aged 1 month to 6 years received sapropterin dihydrochloride 20 mg/kg per day for 6 months. Adverse reactions in these patients were similar in frequency and type as those seen in other sapropterin dihydrochloride 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 (5.3), Pediatric Use (8.4), and Clinical Studies (14)] .

In Study 6, a long term, open-label, extension study of 111 patients aged 4 to 50 years, receiving Sapropterin dihydrochloride 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 Sapropterin dihydrochloride 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). In Study 7, 27 pediatric patients with PKU aged 0 to 4 years received sapropterin dihydrochloride 10 mg/kg per day or 20 mg/kg per day. Adverse reactions were similar in type and frequency to those observed in other clinical trials, with the addition of rhinitis, which was reported in 2 subjects (7.4%). Safety Experience from Clinical Studies for Non-PKU Indications Approximately 800 healthy subjects 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 seizures, exacerbation of seizures [see Warnings and Precautions (5.3)] , 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. 6.2. Postmarketing Experience The following adverse reactions have been reported during post-approval use of sapropterin dihydrochloride. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Hypersensitivity reactions including anaphylaxis and rash : Most hypersensitivity reactions occurred within several days of initiating treatment [see Warnings and Precautions (5.1)] . Gastrointestinal reactions: esophagitis, gastritis, oropharyngeal pain, pharyngitis, esophageal pain, abdominal pain, dyspepsia, nausea, and vomiting [see Warnings and Precautions (5.2)] . Hyperactivity : Two cases have been reported. In one case, the patient received an accidental overdosage of sapropterin dihydrochloride tablets [see Warnings and Precautions (5.6), Overdosage (10)].

Sapropterin Dihydrochloride

Indications

Contraindications

Warnings and precautions

At a glance

Two medicines in one question?

Sapropterin Dihydrochloride

Indications

Contraindications

Warnings and precautions

At a glance

Two medicines in one question?

Interactions

Adverse reactions

Composition

Strengths and forms

Official product information