Ogsiveo inhibits the activation of Notch receptors by suppressing γ-secretase, thereby interfering with certain cellular signaling pathways and inhibiting the proliferation of tumor cells. It has not yet been launched in China. 

Defibrotide(Defitelio):Clinical Uses, Recommended Dosage, Treatment Effect

This article provides a detailed account of Ogsiveo, including its indications, usage and dosage, side effects, contraindications, and clinical efficacy.

(I) Indications

Ogsiveo is indicated for adult patients with progressive desmoid tumors requiring systemic treatment. As a γ-secretase inhibitor, the drug is applicable to lesions that are inoperable or have recurred and progressed after surgery.

(II) Usage and Dosage

Recommended Dosage

The recommended dosage is 150mg taken orally twice a day, until the disease progresses or unacceptable adverse reactions occur. Each 150mg dose can be composed of three 50mg tablets or one 150mg tablet. It can be taken with food or on an empty stomach.

Patients are instructed to swallow the tablets whole; they must not be chewed, crushed, or broken. If a dose is missed or vomiting occurs, the missed dose should not be made up, and the next dose should be taken at the regular time.

Dosage Adjustment for Adverse Reactions

Severe diarrhea (Grade 3-4) lasting for more than 3 days:

Discontinue the drug. After the symptoms subside to Grade 1 or return to the baseline, resume treatment at 100mg twice a day.

Elevated transaminases (ALT/AST):

Grade 2 (3-5×ULN): Discontinue the drug until the levels return to <3×ULN or the baseline, then resume at 100mg twice a day.

Grade 3 or 4 (>5×ULN): Discontinue the drug permanently.

Hypophosphatemia or hypokalemia (Grade 3-4):

If the condition persists for ≥3 days despite maximum efforts of replacement therapy, discontinue the drug until the electrolytes return to normal or Grade 1, then resume at 100mg twice a day.

(III) Target Population

Adults. Pregnant and lactating women, children, and elderly patients should use the drug under the guidance of a doctor.

(IV) Contraindications

Currently, there are no clearly specified contraindications in the Ogsiveo package insert.

(V) Side Effects

The most common adverse reactions (≥15%)

Digestive system: diarrhea, nausea, stomatitis, abdominal pain;

Reproductive system: ovarian toxicity (in female patients);

Skin-related: rash, alopecia;

Nervous system: headache;

Respiratory system: cough, dyspnea;

Systemic: fatigue, upper respiratory tract infection;

Laboratory abnormalities: hypophosphatemia, increased urine glucose, increased urine protein, elevated transaminases, hypokalemia.

Severe adverse reactions

Ovarian toxicity, severe diarrhea, hepatotoxicity, etc.

(VI) Precautions

Diarrhea

Severe diarrhea may occur. It is recommended to conduct regular monitoring, use anti-diarrheal drugs, and adjust the dosage of Ogsiveo if necessary.

Ovarian toxicity

It may cause damage to female fertility. Patients should be informed of the fertility risks before treatment, and changes in the menstrual cycle and symptoms of estrogen deficiency should be monitored during treatment.

Hepatotoxicity

Elevations in AST and ALT are common, so regular monitoring of liver function is required.

Non-melanoma skin cancer

A small number of patients develop squamous cell carcinoma and basal cell carcinoma. Regular skin examinations should be performed before and during treatment.

Electrolyte disorders

Including hypophosphatemia and hypokalemia, which require regular monitoring and timely supplementation.

Embryo-fetal toxicity

Animal studies have shown that it has teratogenic effects on the fetus, so Ogsiveo is contraindicated during pregnancy. Patients of childbearing potential are advised to take effective contraceptive measures.

(VII) Therapeutic Effect

Clinical studies have shown that Ogsiveo has significant clinical benefits in prolonging progression-free survival and improving the objective response rate, and also excels in improving patient-reported outcomes such as pain.

(VIII) Drug Interactions

Effects of other drugs on Ogsiveo

CYP3A inhibitors (e.g., itraconazole): significantly increase the blood drug concentration, and concurrent use should be avoided.

CYP3A inducers (e.g., rifampicin): significantly reduce drug exposure, which may decrease efficacy, and concurrent use should be avoided.

Gastric acid inhibitors (e.g., PPI and H2RA): may reduce drug absorption. If unavoidable, they should be taken 2 hours apart from antacids.

Effects of Ogsiveo on other drugs

Drugs that are CYP3A substrates: Ogsiveo can increase their blood concentrations, which may increase toxicity, so concurrent use should be avoided.

Drugs that are CYP2C19 substrates: Ogsiveo can reduce their exposure, affecting efficacy, so concurrent use should be done with caution.

(IX) Storage Conditions

Store at 20°C-25°C (68°F-77°F), with a permissible short-term fluctuation range of 15°C-30°C (59°F-86°F).

【Warm Reminder】: The instructions for some products are updated frequently; please refer to the actual product.