FDA

Fensolvi Kit

Approved 1 May 2020SubcutaneousPowder

Indications

FENSOLVI is indicated for the treatment of pediatric patients 2 years of age and older with central precocious puberty (CPP). FENSOLVI is a gonadotropin releasing hormone (GnRH) agonist indicated for the treatment of pediatric patients 2 years of age and older with central precocious puberty.

Contraindications

Hypersensitivity to GnRH, GnRH agonists or any of the components of FENSOLVI. Anaphylactic reactions to synthetic GnRH or GnRH agonists have been reported [see Adverse Reactions ( 6.2 )] . Pregnancy: FENSOLVI may cause fetal harm [see Use in Specific Populations ( 8.1 )] . Hypersensitivity reactions ( 4 ) Pregnancy ( 4 , 8.1 )

Warnings and precautions

Initial Rise of Gonadotropins and Sex Steroid Levels: During the early phase of therapy, gonadotropins and sex steroids rise above baseline because of the initial stimulatory effect of the drug. Therefore, an increase in clinical signs and symptoms of puberty including vaginal bleeding may be observed during the first weeks of therapy or after subsequent doses. Instruct patients and caregivers to notify the physician if these symptoms continue beyond the second month after FENSOLVI administration.

( 5.1 ) 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 ) Pseudotumor Cerebri (Idiopathic Intracranial Hypertension): Have been reported in pediatric patients receiving GnRH agonists, including leuprolide acetate. Monitor patients for headache, papilledema, and blurred vision. ( 5.4 )

5.1 Initial Rise of Gonadotropins and Sex Steroid Levels During the early phase of therapy, gonadotropins and sex steroids rise above baseline because of the initial stimulatory effect of the drug [see Clinical Pharmacology ( 12.2 )] . Therefore, an increase in clinical signs and symptoms of puberty including vaginal bleeding may be observed during the first weeks of therapy or after subsequent doses [see Adverse Reactions (6) ] .

Instruct patients and caregivers to notify the physician if these symptoms continue beyond the second month after FENSOLVI administration.

At a glance

Brand name: Fensolvi Kit
Active substance: leuprolide acetate
Route: Subcutaneous
Dosage form: Powder
Applicant: Tolmar
Status: Prescription
FDA approval: 1 May 2020
Application: NDA213150-001

Contraindications

Warnings and precautions

Instruct patients and caregivers to notify the physician if these symptoms continue beyond the second month after FENSOLVI administration.

Pregnancy and breastfeeding

8.1Pregnancy Risk Summary

FENSOLVI is contraindicated in pregnancy [see Contraindications ( 4 )] . FENSOLVI may cause fetal harm based on findings from animal studies and the drug’s mechanism of action [see Clinical Pharmacology ( 12.1 )]. The available data from published clinical studies and case reports and from the pharmacovigilance database on exposure to leuprolide acetate during pregnancy are insufficient to assess the risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes.

Based on animal reproduction studies, leuprolide acetate may be associated with an increased risk of pregnancy complications, including early pregnancy loss and fetal harm. In animal reproduction studies, subcutaneous administration of leuprolide acetate to rabbits during the period of organogenesis caused embryo-fetal toxicity, decreased fetal weights and a dose-dependent increase in major fetal abnormalities in animals at doses less than the recommended human dose based on body surface area using an estimated daily dose.

A similar rat study also showed increased fetal mortality and decreased fetal weights but no major fetal abnormalities at doses less than the recommended human dose based on body surface area using an estimated daily dose (see Data) . 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% to 4% and 15% to 20%, respectively.

Data Animal Data When administered on day 6 of pregnancy at test dosages of 0.00024 mg/kg, 0.0024 mg/kg, and 0.024 mg/kg (1/3255 to 1/33 of the human dose) to rabbits, leuprolide acetate produced a dose-related increase in major fetal abnormalities. Similar studies in rats failed to demonstrate an increase in fetal malformations. There was increased fetal mortality and decreased fetal weights with the two higher doses of leuprolide acetate in rabbits and with the highest dose (0.024 mg/kg) in rats.

Adverse reactions

The following serious adverse reactions are described here and elsewhere in the label: Initial rise in gonadotropin and sex steroid levels [see Warnings and Precautions ( 5.1 )] . Psychiatric Events [see Warnings and Precautions ( 5.2 )] . Convulsions [see Warnings and Precautions ( 5.3 )] . Pseudotumor Cerebri (Idiopathic Intracranial Hypertension) [ see Warnings and Precautions ( 5.4 )] The most common adverse reactions (≥5%) were: injection site pain, nasopharyngitis, pyrexia, headache, cough, abdominal pain, injection site erythema, nausea, constipation, vomiting, upper respiratory tract infection, bronchospasm, productive cough, and hot flush.

( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Tolmar Pharmaceuticals, Inc. at 1-844-4TOLMAR (1-844-486-5627) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

6.1Clinical Trials Experience

Because clinical studies 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. FENSOLVI was evaluated in an uncontrolled, open-label, single-arm clinical trial in which 64 pediatric patients with CPP received at least one dose of FENSOLVI.

The age ranged from 4 to 9 years at start of treatment; 62 patients were female and 2 were male; 53% White; 23% Black; 8% American Indian or Alaska Native; 5% Asian; 2% Native Hawaiian or Other Pacific Islander. 56% of the subjects self-identified as Hispanic or Latino ethnicity. Adverse reactions that occurred in ≥ 5% of patients are shown in Table 2. Table 2: Adverse Reactions Occurring in ≥ 5% of Patients Treated with FENSOLVI in an Open-Label, Single-Arm Trial Adverse Reactions % of Patients (N=64) Injection site pain 31 Nasopharyngitis 22 Pyrexia 17 Headache 16 Cough 13 Abdominal pain 9 Injection site erythema 9 Nausea 8 Constipation 6 Vomiting 6 Upper respiratory tract infection 6 Bronchospasm 6 Productive cough 6 Hot flush 5 Other Adverse Reactions: Psychiatric Emotional disorder (2%) and irritability (2%)

6.2Postmarketing Experience

The following adverse reactions have been identifed during postapproval use of leuprolide acetate or FENSOLVI. 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. Allergic Reactions: anaphylactic, rash, urticaria, and photosensitivity reactions. General : chest pain, weight increase, weight decrease, decreased appetite, fatigue.

Laboratory Abnormalities: decreased WBC. Metabolic : diabetes mellitus. Musculoskeletal and Connective Tissue : arthralgia, epiphysiolysis, muscle spasms, myalgia. Neurologic: neuropathy peripheral, convulsion, paralysis, insomnia, pseudotumor cerebri (idiopathic intracranial hypertension). Psychiatric: emotional lability, such as crying, irritability, impatience, anger and aggression. Depression, including rare reports of suicidal ideation and attempt.

Many, but not all, of these patients had a history of psychiatric illness or other comorbidities with an increased risk of depression. Skin and Subcutaneous Tissue : injection site reactions including induration and abscess, flushing, hyperhidrosis. Reproductive System: vaginal bleeding, breast enlargement. Vascular : hypertension, hypotension. Respiratory: dyspnea.

Fensolvi Kit

Indications

Contraindications

Warnings and precautions

At a glance

Two medicines in one question?

Fensolvi Kit

Indications

Contraindications

Warnings and precautions

At a glance

Two medicines in one question?

5.2Psychiatric Events

5.3Convulsions

5.4Pseudotumor Cerebri (Idiopathic Intracranial Hypertension)

Interactions

Pregnancy and breastfeeding

8.1Pregnancy Risk Summary

Adverse reactions

6.1Clinical Trials Experience

6.2Postmarketing Experience

Composition

Official product information