Fensolvi

Dosing Information

FENSOLVI must be administered by a healthcare provider.

The dose of FENSOLVI is 45 mg administered by subcutaneous injection once every six months.

Discontinue FENSOLVI treatment at the appropriate age of onset of puberty.

Monitoring

Monitor response to FENSOLVI with a GnRH agonist stimulation test, basal serum luteinizing hormone (LH) levels or serum concentration of sex steroid levels at 1 to 2 months following initiation of therapy and as needed to confirm adequate suppression of pituitary gonadotropins, sex steroids, and progression of secondary sexual characteristics. Measure height (for calculation of growth velocity) every 3 to 6 months and monitor bone age periodically.

Noncompliance with drug regimen or inadequate dosing may lead to gonadotropins and/or sex steroids increasing above prepubertal levels resulting in inadequate control of the pubertal process. If the dose of FENSOLVI is not adequate, switching to an alternative GnRH agonist for the treatment of CPP with the ability for dose adjustment may be necessary.

 Reconstitution Instructions

Use aseptic technique including gloves for reconstitution and administration. Allow the product to reach room temperature before reconstitution to allow for easier administration. Once reconstituted, the concentration is 45 mg/0.375 mL. Administer the product within 30 minutes or discard.

FENSOLVI is packaged in a carton containing:

• Tray containing pre-connected syringe system and desiccant pack
• Prescribing information
• Sterile safety needle and cap (located under the tray in carton)

Follow the detailed instructions below to ensure correct preparation of FENSOLVI prior to administration:

Step 1 On a clean field open the tray by tearing off the foil from the corner and remove the contents. Discard the desiccant pack. Remove the pre-connected syringe system from the tray. Open the sterile safety needle package by peeling back the paper tab. Note: Syringe A and Syringe B should not be lined-up yet. The product should only be administered with the co-packaged, sterile safety needle.
Step 2 Grasp the latching button on the coupling device with your finger and thumb and press until you hear a snapping sound. The two syringes will be aligned. Do not bend the pre-connected syringe system.
Step 3 Holding the syringes in a horizontal position, transfer the liquid contents of Syringe A into the leuprolide acetate powder contained in Syringe B. Thoroughly mix the product for 60 cycles by pushing the contents back and forth between both syringes to obtain a uniform suspension. A cycle is one push of the Syringe A plunger and one push of the Syringe B plunger. When thoroughly mixed, the suspension will appear colorless to pale yellow. Note: Product must be mixed as described; shaking will NOT provide adequate mixing. Do not bend.
Step 4 After mixing, hold the syringes vertically (upright) with Syringe B (wide syringe) on the bottom. The syringes should remain securely coupled. Transfer all of the mixed product into Syringe B by depressing the Syringe A plunger and slightly withdrawing the Syringe B plunger.
Step 5 While ensuring the Syringe A plunger is fully pushed down, hold the coupling device and unscrew Syringe B. This will disconnect Syringe B from the coupling device. Syringe A will remain attached to the coupling device. Note: Small air bubbles will remain in the formulation – this is acceptable. Do not purge the air bubbles from Syringe B as product may be lost!
Step 6 Continue to hold Syringe B upright with the open end at the top. Hold back the white plunger on Syringe B to prevent loss of the product, and attach the safety needle and cap (the safety needle is located under the tray). Gently screw clockwise with approximately a three-quarter turn until the safety needle and cap are secure. Do not overtighten, as the needle hub may become damaged which could result in leakage of the product during injection. The safety shield may also be damaged if the safety needle and cap are screwed with too much force.
Step 7 Move the safety shield away from the needle and towards the syringe. Pull off the cap immediately prior to administration.

Note: Should the needle hub appear to be damaged, or leak, do not use the product. If the needle hub is damaged or leakage is observed, use a new FENSOLVI carton.

Administration Instructions

1. Select an injection site on the abdomen, upper buttocks, or another location with adequate amounts of subcutaneous tissue that does not have excessive pigment, nodules, lesions, or hair and hasn’t recently been used. 2. Cleanse the injection-site area with an alcohol swab (not enclosed). 3. Using the thumb and forefinger, grab and bunch the area of skin around the injection site.
4. Using your dominant hand, insert the needle quickly at a 90° angle to the skin surface. The depth of penetration will depend on the amount and fullness of the subcutaneous tissue and the length of the needle. After the needle is inserted, release the skin. 5. Inject the drug using a slow, steady push and press down on the plunger until the syringe is empty. Make sure all the drug has been injected before removing the needle. 6. Withdraw the needle quickly at the same 90° angle used for insertion.
7. Immediately following the withdrawal of the needle, activate the safety shield using a finger/thumb or flat surface and push until it completely covers the needle tip and locks into place. 8. An audible and tactile “click” verifies a locked position. 9. Check to confirm the safety shield is fully engaged. Discard all components safely in an appropriate biohazard container.

Pregnancy

Risk Summary

FENSOLVI is contraindicated in pregnancy [see Contraindications ].

FENSOLVI may cause fetal harm based on findings from animal studies and the drug’s mechanism of action [see Clinical Pharmacology ]. 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.

Lactation

Risk Summary

There are no data on the presence of leuprolide acetate in either animal or human milk, the effects on the breastfed infants, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for FENSOLVI and any potential adverse reactions on the breastfed infant from FENSOLVI or from the underlying maternal condition.

Femalesand Males of Reproductive Potential

Pregnancy Testing

Exclude pregnancy in women of reproductive potential prior to initiating FENSOLVI if clinically indicated [see Use in Specific Populations ].

Contraception

Females

FENSOLVI may cause embryo-fetal harm when administered during pregnancy. FENSOLVI is not a contraceptive. If contraception is indicated, advise females of reproductive potential to use a non-hormonal method of contraception during treatment with FENSOLVI [see Use in Specific Populations ].

Infertility

Based on its pharmacodynamic effects of decreasing secretion of gonadal steroids, fertility is expected to be decreased while on treatment with FENSOLVI. Clinical and pharmacologic studies in adults (>18 years) with leuprolide acetate and similar analogs have shown reversibility of fertility suppression when the drug is discontinued after continuous administration for periods of up to 24 weeks [see Clinical Pharmacology ].

There is no evidence that pregnancy rates are affected following discontinuation of FENSOLVI.

Animal studies (prepubertal and adult rats and monkeys) with leuprolide acetate and other GnRH analogs have shown functional recovery of fertility suppression.

Pediatric Use

The safety and effectiveness of FENSOLVI for the treatment of CPP has been established in pediatric patients 2 years of age and older. Use of FENSOLVI for this indication is supported by evidence from an adequate and uncontrolled open-label, single-arm study of 64 pediatric patients with CPP with an age range of 4 to 9 years [see Clinical Studies ]. The safety and effectiveness of FENSOLVI have not been established in pediatric patients less than 2 years old.

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 ]. 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.

Psychiatric Events

Psychiatric events have been reported in patients taking GnRH agonists, including leuprolide acetate. 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 FENSOLVI [see Adverse Reactions (6.1,  6.2)].

Convulsions

Postmarketing reports of convulsions have been observed in patients receiving GnRH agonists, including leuprolide acetate. 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 [see Adverse Reactions (6.2)].

 PseudotumorCerebri (Idiopathic Intracranial Hypertension)

Pseudotumor cerebri (idiopathic intracranial hypertension) have been reported in pediatric patients receiving GnRH agonists, including leuprolide acetate. Monitor patients for signs and symptoms of pseudotumor cerebri, including headache, papilledema, blurred vision, diplopia, loss of vision, pain behind the eye or pain with eye movement, tinnitus, dizziness, and nausea [see Adverse Reactions  ( 6.2 )].