Paribac 100 mg (Capsule)

Indications

• Maintenance treatment of recurrent epithelial ovarian cancer
• Maintenance treatment of fallopian tube cancer
• Maintenance treatment of primary peritoneal cancer
• Complete or partial response to platinum-based chemotherapy

Pharmacology

• Inhibitor of poly (ADP-ribose) polymerase (PARP) enzymes
• Role in DNA repair
• Induced cytotoxicity involving inhibition of PARP enzymatic activity
• Increased formation of PARP-DNA complexes resulting in DNA damage
• Apoptosis and cell death
• Increased cytotoxicity in tumor cell lines with or without BRCA1/2 deficiencies
• Decreased tumor growth in mouse xenograft models
• Decreased tumor growth in human patient-derived xenograft tumor models with homologous recombination deficiency
• Bioavailability of approximately 73%
• Peak plasma concentration reached within 3 hours
• Binding to human plasma proteins at 83.0%
• Apparent volume of distribution (Vd/F) was 1220 L
• Mean half-life (t1/2) is 36 hours
• Metabolized primarily by carboxylesterases (CEs)
• Excretion in urine and feces

Dosage & Administration

• Recommended dose of 300 mg as monotherapy
• Oral administration once daily
• Swallowed whole with water
• Taken with or without food
• Bedtime administration as a potential method for managing nausea
• Start no later than 8 weeks after most recent platinum-containing regimen
• Treatment continued until disease progression or unacceptable toxicity
• Missed dose instructions
• Bedtime administration as a potential method for managing nausea

Interaction

• Inhibition of CYPs (CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A4)
• Caution when combined with CYP3A4-dependent active substances
• Induction of CYPs (CYP1A2, CYP3A4)
• Caution when combined with CYP1A2-dependent active substances

Contraindications

• Hypersensitivity to the active substance or excipients
• Breast-feeding

Side Effects

• ADRs occurring > 10% of patients
• Common serious adverse reactions
• Nausea
• Thrombocytopenia
• Fatigue/asthenia
• Anaemia
• Constipation
• Vomiting
• Abdominal pain
• Neutropenia
• Insomnia
• Headache
• Decreased appetite
• Nasopharyngitis
• Diarrhea
• Dyspnea
• Hypertension
• Dyspepsia
• Back pain
• Dizziness
• Cough
• Urinary tract infection
• Arthralgia
• Palpitations
• Dysgeusia

Pregnancy & Lactation

• Pregnancy test requirement for women of childbearing potential prior to treatment
• Effective contraception during therapy and for 1 month after last dose
• No data from use in pregnant women
• Animal reproductive and developmental toxicity
• Contradicted during pregnancy
• Breast-feeding contraindicated
• No clinical data on fertility

Precautions & Warnings

• Myelodysplastic syndrome/acute myeloid leukaemia (MDS/AML) risk
• Incidence in patients receiving Paribac
• Hypertension risk, including hypertensive crisis
• Blood pressure monitoring
• Pregnancy/contraception precautions
• Lactose intolerance caution
• Tartrazine (E102) allergic reaction risk

Use in Special Populations

• Elderly dose adjustment not necessary
• Limited clinical data in patients aged 75 or over
• Safety and efficacy not established in children and adolescents below 18 years
• No dose adjustment for mild to moderate renal impairment
• Data not available for severe renal impairment or end-stage renal disease
• No dose adjustment for mild to moderate hepatic impairment
• No data for severe hepatic impairment

Overdose Effects

• No specific treatment in the event of Paribac overdose
• Physicians should follow general supportive measures
• Symptomatic treatment

Therapeutic Class

• Cytotoxic Chemotherapy

Storage Conditions

• Store in a cool and dry place
• Do not store above 30°C
• Do not take if exposed to temperatures greater than 40°C or 104°F
• Keep out of reach and sight of children

Related Brands

• Paribac 100 mg (Capsule) - ziska-pharmaceuticals-ltd