SYNRIBO Powder for solution for injection Ref.[10354] Active ingredients: Omacetaxine mepesuccinate

2.1 Induction Schedule

The recommended starting schedule for induction is 1.25 mg/m² administered subcutaneously twice daily at approximately 12 hour intervals for 14 consecutive days every 28 days, over a 28-day cycle. Cycles should be repeated every 28 days until patients achieve a hematologic response.

2.2 Maintenance Dosing

The recommended maintenance schedule is 1.25 mg/m² administered subcutaneously twice daily at approximately 12 hour intervals for 7 consecutive days every 28 days, over a 28-day cycle. Treatment should continue as long as patients are clinically benefiting from therapy.

2.3 Dose Adjustments and Modifications

Hematologic Toxicity

SYNRIBO treatment cycles may be delayed and/or the number of days of dosing during the cycle reduced for hematologic toxicities (e.g. neutropenia, thrombocytopenia) [see Warnings and Precautions (5.1)].

Perform complete blood counts (CBCs) weekly during induction and initial maintenance cycles. After initial maintenance cycles, monitor CBCs every two weeks or as clinically indicated. If a patient experiences Grade 4 neutropenia (absolute neutrophil count (ANC) less than 0.5 × 10⁹/L) or Grade 3 thrombocytopenia (platelet counts less than 50 × 10⁹/L) during a cycle, delay starting the next cycle until ANC is greater than or equal to 1.0 × 10⁹/L and platelet count is greater than or equal to 50 × 10⁹/L. Also, for the next cycle, reduce the number of dosing days by 2 days (e.g. to 12 or 5 days).

Non-Hematologic Toxicity

Manage other clinically significant non-hematologic toxicity symptomatically. Interrupt and/or delay SYNRIBO until toxicity is resolved.

2.4 Reconstitution Instructions and Handling Precautions

SYNRIBO should be prepared in a healthcare facility and must be reconstituted by a healthcare professional.

Reconstitute SYNRIBO with one mL of 0.9% Sodium Chloride Injection, USP, prior to subcutaneous injection. After addition of the diluent, gently swirl until a clear solution is obtained. The lyophilized powder should be completely dissolved in less than one minute. The resulting solution is clear and colorless and contains 3.5 mg/mL SYNRIBO. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.

SYNRIBO does not contain antimicrobial preservatives. Therefore care must be taken to ensure that the solution for injection is not contaminated during preparation.

SYNRIBO is a cytotoxic drug. Follow special handling and disposal procedures¹. Wear protective eyewear and gloves during handling and administration of the product. Proper aseptic technique should be used. Avoid skin and eye contact. If SYNRIBO comes into contact with skin, immediately and thoroughly wash affected area with soap and water. If contact with the eyes occurs, thoroughly flush the eyes with water.

2.5 Storage Conditions and Storage Time after Preparation of Syringes

If SYNRIBO is not used immediately after reconstitution, follow in-use storage conditions and allowable storage times prior to use as instructed in Table 1. Do not administer SYNRIBO outside of the storage conditions and timeframes listed in Table 1.

Table 1. Storage Conditions and Storage Time after Preparation of Syringes:

2.6 Considerations for Home Administration

Before a decision is made to allow SYNRIBO to be administered by someone other than a healthcare professional, ensure that the patient is an appropriate candidate for self-administration or for administration by a caregiver. Provide training on proper handling, storage conditions, administration, disposal, and clean-up of accidental spillage of the product. Ensure that patients receive the necessary supplies for home administration. At minimum these should include:

• Reconstituted SYNRIBO in syringe with a capped needle for subcutaneous injection. Syringe(s) should be filled to the patient-specific dose.
• Protective eyewear
• Gloves
• An appropriate biohazard container
• Absorbent pad(s) for placement of administration materials and for accidental spillage
• Alcohol swabs
• Gauze pads
• Ice packs or cooler for transportation of reconstituted SYNRIBO syringes

If a patient or caregiver cannot be trained for any reason, then in such patients, SYNRIBO should be administered by a healthcare professional.

2.7 Disposal and Accidental Spillage Procedures

After administration, any unused solution should be discarded properly¹. Instruct patients planning home administration on the following: do not recap or clip the used needle, and do not place used needles, syringes, vials, and other used supplies in a household trash or recycling bin. Used needles, syringes, vials, and other used supplies should be disposed of in an appropriate biohazard container.

If accidental spillage occurs, continue to use protective eyewear and gloves, wipe the spilled liquid with the absorbent pad, and wash the area with water and soap. Then, place the pad and gloves into the biohazard container and wash hands thoroughly. Return the biohazard container to the clinic or pharmacy for final disposal.

A patient in the clinical expanded access program received an overdose of 2.5 mg/m² twice daily for 5 days in the 16^th cycle. The patient presented with gastrointestinal disorders, gingival hemorrhage, alopecia, and Grade 4 thrombocytopenia and neutropenia. When SYNRIBO treatment was temporarily interrupted the gastrointestinal disorders and hemorrhagic syndrome resolved, and neutrophil values returned to within normal range. The alopecia and thrombocytopenia (Grade 1) improved, and SYNRIBO was restarted.

No specific antidote for SYNRIBO overdose is known. Management of overdosage should include general supportive measures, including monitoring of hematologic parameters.

Store unopened vials at 20ºC to 25ºC (68ºF to 77ºF); excursions permitted from 15ºC to 30ºC (59ºF to 86ºF) [see USP Controlled Room Temperature]. Prior to re-constitution, keep product in carton to protect from light.

Omacetaxine mepesuccinate is a cytotoxic drug. Follow special handling and disposal procedures¹.