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DRUGS & SUPPLEMENTS
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Diphereline PR
How long you have been taking the medicine? |
Diphereline PR uses
- Indications and usage
- Dosage and administration
- Dosage forms and strengths
- Contraindications
- Warnings and precautions
- Adverse reactions
- Drug interactions
- Use in specific populations
- Overdosage
- Description
- Clinical pharmacology
- Nonclinical toxicology
- Clinical studies
- How supplied/storage and handling
- Patient counseling information
1 INDICATIONS AND USAGE
Diphereline PR is indicated for the treatment of pediatric patients 2 years of age and older with central precocious puberty (CPP).
Diphereline PR is a gonadotropin releasing hormone (GnRH) agonist indicated for the treatment of pediatric patients 2 years and older with central precocious puberty. (1)
2 DOSAGE AND ADMINISTRATION
- Must be administered under the supervision of a physician.
- Administer Diphereline PR as a single intramuscular injection of 22.5 mg once every 24 weeks. (2.1)
- Monitor response with LH levels after a GnRH or GnRH agonist stimulation test, basal LH, or serum concentration of sex steroid levels beginning 1 to 2 months following initiation of therapy, during therapy as necessary to confirm maintenance of efficacy, and with each subsequent dose. (2.2)
- Measure height every 3-6 months and monitor bone age periodically. (2.2)
- See FPI for reconstitution and administration instructions. (2.3)
2.1 Dosing Information
Diphereline PR must be administered under the supervision of a physician.
The dosage of Diphereline PR is 22.5 mg reconstituted with accompanying diluent (Sterile Water) 2 mL, and administered as a single intramuscular injection once every 24 weeks.
Diphereline PR treatment should be discontinued at the appropriate age of onset of puberty at the discretion of the physician.
2.2 Monitoring
Monitor response to Diphereline PR with LH levels after a GnRH or GnRH agonist stimulation test, basal LH, or serum concentration of sex steroid levels beginning 1 to 2 months following initiation of therapy, during therapy as necessary to confirm maintenance of efficacy, and with each subsequent dose.
Measure height every 3-6 months and monitor bone age periodically.
Noncompliance with drug regimen or inadequate dosing may result in inadequate control of the pubertal process with gonadotropins and/or sex steroids increasing above prepubertal levels. If the dose of Diphereline PR is not adequate switching to an alternative GnRH agonist for the treatment of CPP with the ability for dose adjustment may be necessary.
2.3 Reconstitution and Administration Instructions
Please read these instructions completely before you begin.
- Use appropriate aseptic technique for preparation and administration.
- Screw the plunger rod into the barrel end of the prefilled sterile water diluent syringe.
- Remove the cap from the syringe barrel.
- Firmly attach one of the 21-gauge sterile safety needles onto the prefilled sterile water diluent syringe with a push and clockwise twist. This 21-gauge needle will only be used for reconstitution of the product.
- Pull back on the safety cover towards the syringe and away from the 21-gauge needle. Then pull the clear needle shield off.
- Insert the 21-gauge needle to inject the Sterile Water diluent into the vial. Do not release the plunger rod. Gently swirl the vial ensuring the diluent rinses the sides of the vial. The reconstituted solution is a milky suspension.
Important: Once mixed, proceed to the next steps and administer without delay.
- Invert the vial and move back the syringe in order to position the end of the 21-gauge needle very near the level of the stopper, making sure the needle lumen is still completely in the vial.
- Pull back the plunger rod slowly to withdraw the reconstituted product into the syringe, withdrawing as much of the reconstituted product into the syringe as possible.
- Push the safety cover forward toward the needle until you hear and/or feel it lock. Then remove the first 21-gauge needle by grasping the needle hub to disconnect the needle from the syringe and discard it. This (first) 21-gauge needle will no longer be used.
- Firmly attach the second sterile needle onto the syringe and pull back the safety cover towards the syringe. This 21-gauge needle will be used for administration.
- Prime the 21-gauge needle to first remove air from the syringe, inspect the suspension visually for particulate matter and discoloration. If the suspension appears milky and homogenous without visible aggregates or precipitates then administer the suspension immediately.
- Inject the patient preferably in either buttock or thigh using the entire contents of the syringe.
- The injection of the suspension should be performed relatively rapidly and in a steady and uninterrupted manner in order to avoid any potential blockage of the needle.
After administering the injection, immediately activate the safety cover:
- Center your thumb or forefinger on the textured finger pad area of the safety cover and push it forward over the needle until you hear or feel it lock.
- Use the one-handed technique and activate the mechanism away from yourself and others.
- Immediately discard the syringe assembly into a suitable sharps container.
3 DOSAGE FORMS AND STRENGTHS
For extended-release injectable suspension: 22.5 mg of Diphereline PR as a lyophilized white to slightly yellow powder cake in a single-dose vial for reconstitution with the co-packaged 2 mL of diluent (Sterile Water) for Injection.
For extended-release injectable suspension: 22.5 mg of Diphereline PR as a powder cake for reconstitution with the co-packaged 2 mL of diluent Sterile Water for Injection. (3)
4 CONTRAINDICATIONS
- Hypersensitivity: Diphereline PR is contraindicated in individuals with a known hypersensitivity to Diphereline PR, any other component of the product, or other GnRH agonists or GnRH .
- Pregnancy: Diphereline PR may cause fetal harm .
- Hypersensitivity reactions (4)
- Pregnancy (4, 8.1)
5 WARNINGS AND PRECAUTIONS
- Initial Rise of Gonadotropins and Sex Steroid Levels: An increase in clinical signs and symptoms of puberty may be observed during the first 2- 4 weeks of therapy since gonadotropins and sex steroids rise above baseline because of the initial stimulatory effect of the drug.
- Psychiatric events have been reported in patients taking GnRH agonists. Events include emotional lability, such as crying, irritability, impatience, anger, and aggression. Monitor for development or worsening of psychiatric symptoms. (5.2)
- Convulsions have been observed in patients with or without a history of seizures, epilepsy, cerebrovascular disorders, central nervous system anomalies or tumors, and in patients on concomitant medications that have been associated with convulsions. (5.3)
5.1 Initial Rise of Gonadotropins and Sex Steroid Levels
During the early phase of initial therapy or after subsequent doses, gonadrotropins and sex steroids may rise above baseline because of a transient stimulatory effect of the drug . Therefore, a transient increase in clinical signs and symptoms of puberty, including vaginal bleeding, may be observed during the first weeks of therapy or after subsequent doses.
5.2 Psychiatric Events
Psychiatric events have been reported in patients taking GnRH agonists, including Diphereline PR. Postmarketing reports with this class of drugs include symptoms of emotional lability, such as crying, irritability, impatience, anger, and aggression. Monitor for development or worsening of psychiatric symptoms during treatment with Diphereline PR .
5.3 Convulsions
Postmarketing reports of convulsions have been observed in patients receiving GnRH agonists, including Diphereline PR. These included patients with a history of seizures, epilepsy, cerebrovascular disorders, central nervous system anomalies or tumors, and patients on concomitant medications that have been associated with convulsions such as bupropion and SSRIs. Convulsions have also been reported in patients in the absence of any of the conditions mentioned above .
6 ADVERSE REACTIONS
The following serious adverse reactions are described here and elsewhere in the label:
- Initial Rise of Gonadotropins and Sex Steroid Levels
- Psychiatric Events
- Convulsions
In clinical trials for Diphereline PR, the most common adverse reactions (≥4.5%) are injection site reactions, menstrual (vaginal) bleeding, hot flush, headache, cough, and infections (bronchitis, gastroenteritis, influenza, nasopharyngitis, otitis externa, pharyngitis, sinusitis, and upper respiratory tract infection). (6.1)
To report SUSPECTED ADVERSE REACTIONS, contact Arbor Pharmaceuticals, LLC at 1-866-516-4950 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 rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The safety of Diphereline PR was evaluated in one uncontrolled, open-label single-arm clinical trial in which 44 children with central precocious puberty received two doses of Diphereline PR and were observed for 12 months. The median age of the study population was 8 years (range 2-9 years) at treatment start; 88.6% of subjects were female, 59.1% were White, 27.3% were Black and 4.5% were Asian. Table 1 shows all the adverse reactions that occurred in at least 2 patients (≥4.5%) during the open-label single-arm trial.
| Adverse Reactions | Number of Patients Reporting Event (%) (Total N=44) |
|---|---|
| Infections & Infestations | |
| Bronchitis | 2 (4.5) |
| Gastroenteritis | 3 (6.8) |
| Influenza | 2 (4.5) |
| Nasopharyngitis | 6 (13.6) |
| Otitis externa | 2 (4.5) |
| Pharyngitis | 2 (4.5) |
| Sinusitis | 2 (4.5) |
| Upper respiratory tract infection | 4 (9.1) |
| Nervous System Disorders | |
| Headache | 6 (13.6) |
| Reproductive System & Breast Disorders | |
| Menstrual (Vaginal bleeding) | 3 (7.7) |
| Respiratory, Thoracic & Mediastinal Disorder | |
| Cough | 3 (6.8) |
| Vascular Disorders | |
| Hot flush | 2 (4.5) |
Other Selected Adverse Reactions:
Injection Site Reactions
Injection site reactions occurring in patients immediately and/or 2 hours after injection include pain (45%), redness (14%), pruritus (2.3%) and swelling (2.3%).
Psychiatric Disorders
Anxiety (2.3%) and mood altered (2.3%)
6.2 Postmarketing Experience
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.
The following adverse reactions were reported from postmarketing experience of Diphereline PR in patients with CPP:
Hypersenstivity Reactions: Anaphylactic shock, anaphylactoid reaction, angioedema, urticaria.
Cardiovascular: Hypertension.
Psychiatric: Emotional lability, such as crying, irritability, impatience, anger, and aggression, has been observed with GnRH agonists, including Diphereline PR ; Depression, including rare reports of suicidal ideation and attempt, has been reported for GnRH agonists in children treated for CPP. Many, but not all, of these patients had a history of psychiatric illness or other comorbidities with an increased risk of depression.
Nervous System: Convulsions
Vision Disorders: Visual impairment, visual disturbance
7 DRUG INTERACTIONS
7.1 Drug-Drug Interactions
Results of in vitro studies show that drug-drug interactions with Diphereline PR are unlikely . However, in the absence of relevant data and as a precaution, hyperprolactinemic drugs should not be used concomitantly with Diphereline PR since hyperprolactinemia reduces the number of pituitary GnRH receptors.
7.2 Drug-Laboratory Test Interactions
Administration of Diphereline PR results in suppression of the pituitary-gonadal system.
The effect of Diphereline PR on pituitary and gonadal function is expected to disappear within six to twelve months after treatment discontinuation. Therefore, diagnostic tests of pituitary gonadotropic and gonadal functions conducted during treatment or after discontinuation of treatment may be affected.
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Risk Summary
Diphereline PR is contraindicated in women who are pregnant since expected hormonal changes that occur with Diphereline PR treatment increase the risk for pregnancy loss. Available data with Diphereline PR use in pregnant women are insufficient to determine a drug-associated risk of adverse developmental outcomes. Based on mechanism of action in humans and findings of increased pregnancy loss in animal studies, Diphereline PR may cause fetal harm when administered to pregnant women. Advise pregnant women of the potential risk to a fetus.
The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the US general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% - 4% and 15% -20%, respectively.
Data
Animal Data
In pregnant rats administered Diphereline PR at doses of 2, 10, and 100 mcg/kg/day during the period of organogenesis, maternal toxicity (decrease in body weight) and embryo-fetal toxicities (pre-implantation loss, increased resorption, and reduced number of viable fetuses) were observed at 100 ug/kg, approximately 4 times the clinical dose based on body surface area. No embryonic and fetal developmental toxicities were observed in mice at doses up to 4 times the clinical dose. Teratogenic effects were not observed in viable fetuses in rats or mice.
8.2 Lactation
Risk Summary
There are no data on the presence of Diphereline PR in human milk, or the effects of the drug on the breastfed infant, or on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for Diphereline PR and any potential adverse effects on the breastfed child from Diphereline PR or from the underlying maternal condition.
8.4 Pediatric Use
The safety and effectiveness of Diphereline PR have been established in pediatric patients 2 years of age and older based on a single-arm open-label study of 44 children 2-9 years of age with CPP . The safety and effectiveness of Diphereline PR have not been established in pediatric patients less than 2 years old.
8.6 Renal Impairment
Diphereline PR has not been studied in children with renal impairment. Adult subjects with renal impairment had higher exposure than young healthy adult males .
8.7 Hepatic Impairment
Diphereline PR has not been studied in children with hepatic impairment. Adult subjects with hepatic impairment had higher exposure than young healthy adult males .
10 OVERDOSAGE
There is no experience with overdosage in clinical trials of Diphereline PR. If overdosage occurs, therapy should be discontinued and appropriate supportive and symptomatic treatment administered.
11 DESCRIPTION
Diphereline PR contains the pamoate salt of Diphereline PR, a synthetic decapeptide analog of naturally occurring gonadotropin-releasing hormone (GnRH or LHRH). The chemical name of Diphereline PR pamoate is 5-oxo-L-prolyl-L-histidyl-L-tryptophyl-L-seryl-L-tyrosyl-D-tryptophyl-L-leucyl-L-arginyl-L-prolylglycine amide (pamoate salt). The molecular weight is 1699.9 and the structural formula is:
Diphereline PR for extended release injectable suspension for intramuscular use is provided as a sterile, lyophilized, biodegradable microgranule formulation in a single-dose vial, co-packaged with a syringe containing 2 mL Sterile Water for Injection for reconstitution of the lyophilisate. The Diphereline PR formulation is comprised of 22.5 mg Diphereline PR (equivalent to 31 mg Diphereline PR pamoate), poly-d,l-lactide-co-glycolide (183 mg), mannitol (74 mg), carboxymethylcellulose sodium (26 mg), and polysorbate 80 (1.7 mg). When 2 mL Sterile Water for Injection is added to the vial containing Diphereline PR and mixed, a suspension is formed which is intended as a single intramuscular injection.
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
Diphereline PR is a GnRH agonist.
12.2 Pharmacodynamics
Following the first administration, there is a transient surge in circulating levels of LH, FSH, testosterone, and estradiol . After chronic and continuous administration, by 4 weeks after initiation of therapy, a sustained decrease in LH and FSH secretion and marked reduction in sex steroids are observed.
12.3 Pharmacokinetics
Absorption
After an initial intramuscular Diphereline PR 22.5 mg injection and a second 22.5 mg intramuscular injection 24 weeks later in children 2 to 9 years old with CPP, Diphereline PR peaked 4 hours postdose with a geometric mean Cmax of 39.9 and 36.5 ng/mL, respectively. No apparent accumulation of Diphereline PR occurred after the second injection. Absorption occurred in two phases, a burst phase followed by a maintenance release phase. In children with CPP, following the burst phase after the first 22.5 mg injection, geometric mean serum Diphereline PR levels were 0.11, 0.17, 0.05 and 0.03 ng/mL at Months 1, 2, 3, and 6, respectively.
Distribution
There is no evidence that Diphereline PR, at clinically relevant concentrations, binds to plasma proteins.
Elimination
Metabolism
The metabolism of Diphereline PR in humans is unknown, but is unlikely to involve hepatic microsomal enzymes (cytochrome P450). Thus far no metabolites of Diphereline PR have been identified. Pharmacokinetic data suggest that C-terminal fragments produced by tissue degradation are either completely degraded in the tissues, or rapidly degraded in plasma, or cleared by the kidneys.
Excretion
Diphereline PR is eliminated by both the liver and the kidneys. Following intravenous administration of 0.5 mg Diphereline PR peptide to six healthy male volunteers with a creatinine clearance of 149.9 mL/min, 41.7% of the dose was excreted in urine as intact peptide with a total Diphereline PR clearance of 211.9 mL/min. This percentage increased to 62.3% in patients with liver disease who have a lower creatinine clearance (89.9 mL/min). It has also been observed that the nonrenal clearance of Diphereline PR (patient anuric, Clcreat = 0) was 76.2 mL/min, thus indicating that the nonrenal elimination of Diphereline PR is mainly dependent on the liver.
Specific Populations
Renal Impairment
After intravenous bolus injection of 0.5 mg Diphereline PR in adults, the two distribution half-lives were unaffected by renal impairment. However, renal insufficiency led to a decrease in total Diphereline PR clearance proportional to the decrease in creatinine clearance as well as increases in volume of distribution and consequently, an increase in the elimination half-life. Adult male subjects with moderate or severe renal impairment had approximately 2-fold higher exposure (AUC values) than young healthy adult males .
Hepatic Impairment
After intravenous bolus injection of 0.5 mg Diphereline PR in adults, the two distribution half-lives were unaffected by hepatic impairment. In adult males with hepatic insufficiency, Diphereline PR clearance was reduced and exposure (AUC) was increased 3.7-fold compared to young healthy adult males (Table 2) .
| Group | Cmax (ng/mL) | AUCinf (h∙ng/mL) | Clp (mL/min) | Clrenal (mL/min) | t1/2 (h) | Clcreat (mL/min) |
|---|---|---|---|---|---|---|
| 6 healthy male volunteers | 48.2 ±11.8 | 36.1 ±5.8 | 211.9 ±31.6 | 90.6 ±35.3 | 2.81 ±1.21 | 149.9 ±7.3 |
| 6 males with moderate renal impairment | 45.6 ±20.5 | 69.9 ±24.6 | 120.0 ±45.0 | 23.3 ±17.6 | 6.56 ±1.25 | 39.7 ±22.5 |
| 6 males with severe renal impairment | 46.5 ±14.0 | 88.0 ±18.4 | 88.6 ±19.7 | 4.3 ±2.9 | 7.65 ±1.25 | 8.9 ±6.0 |
| 6 males with liver disease | 54.1 ±5.3 | 131.9 ±18.1 | 57.8 ±8.0 | 35.9 ±5.0 | 7.58 ±1.17 | 89.9 ±15.1 |
Drug-Drug Interactions
In Vitro Assessment of Drug Interactions
Drug Metabolizing Enzyme Inhibition
Diphereline PR did not inhibit CYP1A2, 2B6, 2C8, 2C9, 2C19 or 2D6, or CYP 3A4/5 at clinically relevant concentrations.
Drug Metabolizing Enzyme Induction
In fresh human hepatocytes from three human donors, Diphereline PR did not induce CYP1A2 or CYP3A4/5 activity.
Transporters
Diphereline PR was a poor P-gp substrate and had no inhibitory effect toward P-gp.
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
Carcinogenesis was evaluated in an 18-month study in mice and a 24-month study in rats. In rats, Diphereline PR doses of 120, 600, and 3000 mcg/kg given every 28 days (approximately 0.2, 0.8, and 4 times the estimated human monthly dose based on body surface area) resulted in increased mortality with a drug treatment period of 13 to 19 months. The incidences of benign and malignant pituitary tumors and histosarcomas were increased in a dose-related manner. There were no treatment-related tumors in mice at exposure up to 4-fold higher than the estimated human monthly dose based on body surface area.
Mutagenicity studies performed with Diphereline PR using bacterial and mammalian systems (in vitro Ames test and chromosomal aberration test in CHO cells and an in vivo mouse micronucleus test) provided no evidence of mutagenic potential.
After 60 days of subcutaneous treatment followed by a minimum of four estrus cycles prior to mating, Diphereline PR at doses of 2, 20, and 200 mcg/kg (approximately 0.07, 0.7, and 7 times the estimated human daily dose based on body surface area) or two monthly injections as slow release microspheres (~20 mcg/kg/day) had no effect on the fertility or general reproductive function of female rats.
No studies were conducted to assess the effect of Diphereline PR on male fertility.
14 CLINICAL STUDIES
In a single-arm open-label study, 44 children 2 to 9 years of age with CPP, 39 females and 5 males, all naïve to previous GnRH agonist treatment, were administered Diphereline PR 22.5 mg at a dosing interval of 24 weeks. Subjects were evaluated over two dosing intervals for a total of 12 months.
Diphereline PR 22.5 mg suppressed pituitary release of LH and FSH and, consequently, gonadal secretion of estradiol in girls and testosterone in boys (Table 3). At all timepoints evaluated, ≥93% of children achieved LH suppression to prepubertal levels (i.e., serum LH ≤5 IU/L 30 minutes after GnRH agonist stimulation), ≥79% of girls achieved prepubertal levels of estradiol (i.e., <20 pg/mL), and ≥80% of boys achieved prepubertal levels of testosterone (i.e., <30 ng/dL). Diphereline PR arrested or reversed progression of clinical signs of puberty with 95% of children showing no increase in the bone age/chronological age ratio, and 89% showing stabilization of sexual maturation at Month 12.
| Endpoint | % (n/N) of Children Achieving Endpoint | |||||
|---|---|---|---|---|---|---|
| Month 1 | Month 2 | Month 3 | Month 6 | Month 9 | Month 12 | |
| % with prepubertal LH (GnRH-stim LH ≤5 IU/L) | 95% (42/44) | 95% (42/44) | 95% (42/44) | 93% (41/44) | 95% (42/44) | 98% (43/44) |
| % girls with prepubertal estradiol (<20 pg/mL) | 87% (34/39) | 89% (34/38) | 92% (36/39) | 79% (31/39) | 82% (32/39) | 79% (31/39) |
| % boys with prepubertal testosterone (<30 ng/dL) | 80% (4/5) | 80% (4/5) | 100% (5/5) | 100% (5/5) | 80% (4/5) | 80% (4/5) |
| % with no increase in BA/CA | 64% (28/44) | 95% (42/44) | ||||
| % achieving stabilization of sexual maturation | 91% (40/44) | 89% (39/44) | ||||
| % girls with regression of uterine length | 69% (27/39) | 77% (30/39) | ||||
| % boys with no progression in testis volumes | 100% (5/5) | 100% (5/5) | ||||
Following the second Diphereline PR injection, 22 children (all girls) were assessed for evidence of an acute-on-chronic phenomenon (i.e., increase in basal LH >5 IU/L or serum estradiol level >20 pg/mL 48 hours after the second Diphereline PR injection). Of these, one girl who achieved prepubertal hormone levels prior to the second injection showed biochemical evidence of acute-on-chronic phenomenon .
16 HOW SUPPLIED/STORAGE AND HANDLING
Each Diphereline PR 22.5 mg single-use kit (NDC 24338-150-20) contains:
- One single-dose vial of Diphereline PR 22.5 mg (NDC 24338-150-01) with a Flip-Off seal containing sterile lyophilized white to slightly yellow powder cake
- One sterile, glass syringe with Luer Lock prefilled with 2 mL of Sterile Water for Injection (NDC 24338-150-02)
- Two sterile 21 gauge, 1½" needles (thin-wall) with safety cover
- One Package Insert
Store at 20-25°C (68-77°F). Do not freeze.
17 PATIENT COUNSELING INFORMATION
Advise the patient to read the FDA-approved patient labeling (Patient Information and Medication Guide).
Hypersensitivity Reactions
Inform caregivers that anaphylactic shock, hypersensitivity, and angioedema have been reported with Diphereline PR use and to immediately seek medical attention if any hypersensitivity reaction occurs.
Symptoms after Initial Diphereline PR Administration
Inform caregivers that during the first weeks after the first Diphereline PR injection, signs of puberty may occur such as vaginal bleeding . Caregivers should notify the physician if these symptoms continue beyond the second month after Diphereline PR administration.
Psychiatric Events
Inform caregivers that symptoms of emotional lability, such as crying, irritability, impatience, anger, and aggression have been observed in patients receiving GnRH agonists, including Diphereline PR. Alert caregivers to the possibility of development or worsening of psychiatric symptoms, including depression, during treatment with Diphereline PR .
Convulsions
Inform caregivers that reports of convulsions have been observed in patients receiving GnRH agonists, including Diphereline PR. Patients with a history of seizures, epilepsy, cerebrovascular disorders, central nervous system anomalies or tumors, and patients on concomitant medications that have been associated with convulsions may be at increased risk .
Pregnancy is Contraindicated
Diphereline PR is contraindicated in pregnancy. If the patient becomes pregnant while taking the drug, the patient should be informed of the potential risk to fetus .
Compliance with the Dosing Schedule
Inform caregivers about the importance of adherence to the Diphereline PR dosing schedule of one injection every 24 weeks. Patients should not miss or delay a scheduled dose.
Manufactured for:
Arbor Pharmaceuticals, LLC
Atlanta, GA 30328
Manufactured by:
Debiopharm Research & Manufacturing SA
CH-1920 Martigny, Switzerland
©2017 Arbor Pharmaceuticals, LLC
Diphereline PR is a registered trademark of Arbor Pharmaceuticals, LLC.
Issue: June 2017
TRIP-PI-01
| MEDICATION GUIDE Diphereline PR [TRIP-toe-der] (triptorelin) for extended-release injectable suspension, for intramuscular use | |||
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| This Medication Guide has been approved by the U.S. Food and Drug Administration | Issue: 06/2017 | ||
What is the most important information I should know about Diphereline PR?
Call your child's doctor right away if your child has a seizure while taking Diphereline PR. | |||
What is Diphereline PR?
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Diphereline PR should not be taken if your child is:
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Before your child receives Diphereline PR, tell your child's doctor about all of your child's medical conditions, including if they:
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How will your child receive Diphereline PR?
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| What are the possible side effects of Diphereline PR? Diphereline PR may cause serious side effects. See "What is the most important information I should know about Diphereline PR?" The most common side effects of Diphereline PR include injection site reactions, menstrual (vaginal) bleeding, hot flush, headache, cough, and infections (bronchitis, gastroenteritis, influenza, nasopharyngitis, otitis externa, pharyngitis, sinusitis, and upper respiratory tract infection). These are not all the possible side effects of Diphereline PR. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. | |||
| What are the ingredients in Diphereline PR? Active ingredient: Diphereline PR Inactive ingredients: poly-d,l-lactide-co-glycolide, mannitol, carboxymethylcellulose sodium, and polysorbate 80 Distributed by: Arbor Pharmaceuticals, LLC, Atlanta, GA 30328 Manufactured by: Debiopharm Research & Manufacturing SA, CH-1920 Martigny, Switzerland ©2017 Arbor Pharmaceuticals, LLC All rights reserved. For more information about Diphereline PR, please contact Arbor Pharmaceuticals, LLC at 1-866-516-4950. | |||
Diphereline PR is a registered trademark of Arbor Pharmaceuticals, LLC.
TRIP-MG-01
Diphereline PR pharmaceutical active ingredients containing related brand and generic drugs:
Diphereline PR available forms, composition, doses:
Composition is the list of ingredients which combinedly form a medicine. Both active ingredients and inactive ingredients form the composition. The active ingredient gives the desired therapeutic effect whereas the inactive ingredient helps in making the medicine stable.
Doses are various strengths of the medicine like 10mg, 20mg, 30mg and so on. Each medicine comes in various doses which is decided by the manufacturer, that is, pharmaceutical company. The dose is decided on the severity of the symptom or disease.