tients, Asian patients have an increased risk of severe and febrile neutropenia following treatment with ONIVYDE+5-FU/LV (see sections 4.8 and 5.2).
Immunosuppressive effects and vaccines
Administration of live or live-attenuated vaccines in patients immunocompromised by chemotherapeutic medicinal products including ONIVYDE may result in serious or fatal infections; therefore vaccination with a live vaccine should be avoided. Killed or inactivated vaccines may be administered; however, the response to such vaccines may be diminished.
Interactions with strong CYP3A4 inducers
ONIVYDE should not be administered with strong CYP3A4-enzyme inducers such as anticonvulsants (phenytoin, phenobarbital or carbamazepine), rifampin, rifabutin and St. John's wort unless there are no therapeutic alternatives. The appropriate starting dose for patients taking these anticonvulsants or other strong inducers has not been defined. Consideration should be given to substituting with non-enzyme inducing therapies at least 2 weeks prior to initiation of ONIVYDE therapy (see section 4.5).
Interactions with strong CYP3A4 inhibitors or strong UGT1A1 inhibitors
ONIVYDE should not be administered with strong CYP3A4-enzyme inhibitors (e.g. grapefruit juice, clarithromycin, indinavir, itraconazole, lopinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telaprevir, voriconazole). Strong CYP3A4 inhibitors should be discontinued at least 1 week prior to starting ONIVYDE therapy.
ONIVYDE should not be administered with strong UGT1A inhibitors (e.g. atazanavir, gemfibrozil, indinavir) unless there are no therapeutic alternatives.
Diarrhoea
Diarrhoea can occur early (onset in ≤ 24 hours after starting ONIVYDE) or late (> 24 hours) (see section 4.8).
In patients experiencing early diarrhea, therapeutic and prophylactic atropine should be considered unless contraindicated. Patients should be made aware of the risk of delayed diarrhoea which can be debilitating and, on rare occasions, life threatening since persistent loose or watery stools can result in dehydration, electrolyte imbalance, colitis, gastrointestinal (GI) ulceration, infection or sepsis.
As soon as the first liquid stool occurs, the patient should start drinking large volumes of beverages containing electrolytes. Patients should have loperamide (or equivalent) readily available to begin treatment for late diarrhoea. Loperamide should be initiated at first occurrence of poorly formed or loose stools or at the earliest onset of bowel movements more frequent than normal. Loperamide should be given until patient is without diarrhoea for at least 12 hours.
If diarrhoea persists while patient is on loperamide for more than 24 hours, adding oral antibiotic support (e.g. fluoroquinolone for 7 days) should be considered. Loperamide should not be used for more than 48 consecutive hours due to risk of paralytic ileus. If diarrhoea persists for more than 48 hours, stop loperamide, monitor and replace fluid electrolytes and continue antibiotic support until resolution for accompanying symptoms.
ONIVYDE treatment should be delayed until diarrhoea resolves to ≤ Grade 1 (2-3 stools/day more than pre-treatment frequency). ONIVYDE must not be administered to patients with bowel obstruction, and chronic inflammatory bowel disease, until it is resolved.
Following Grade 3 or 4 diarrhoea, the subsequent dose of ONIVYDE should be reduced, (see section 4.2).
Choliner |
