VENCLAD-treated patients compared to 1% of placebo patients.
Myelodysplastic Syndrome
Cases of myelodysplastic syndrome have been reported in patients that had received parenteralcladribine at a higher dosage than that approved for MAVENCLAD. These cases occurredseveral years after treatment.
Herpes Meningoencephalitis
Fatal herpes meningoencephalitis occurred in one MAVENCLAD-treated patient, at a higherdosage and longer duration of therapy than the approved MAVENCLAD dosage and in
combination with interferon beta-1a treatment.
Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN)SJS and TEN are identified risks of parenteral cladribine for the treatment of oncologic
indications.
Seizures
In clinical studies, serious events of seizure occurred in 0.3% of MAVENCLAD-treated patientscompared to 0 placebo patients. Serious events included generalized tonic-clonic seizures andstatus epilepticus. It is unknown whether these events were related to the effects of multiplesclerosis alone, to MAVENCLAD, or to a combination of both.
7 DRUG INTERACTIONS
Table 3 Drug Interactions with MAVENCLAD
7.1 Immunomodulatory, Immunosuppressive, or Myelosuppressive Drugs
Clinical Impact Concomitant use of MAVENCLAD with immunomodulatory,immunosuppressive, or myelosuppressive drugs may increasethe risk of adverse reactions because of the additive effects onthe immune system [see Warnings and Precautions (5.4)].
Prevention or Management Concomitant use with myelosuppressive or otherimmunosuppressive drugs is not recommended. Acute shorttermtherapy with corticosteroids can be administered.
In patients who have previously been treated withimmunomodulatory or immunosuppressive drugs, considerpotential additive effect, the mode of action, and duration of
effect of the other drugs prior to initiation of MAVENCLAD.
7.2 Interferon-Beta
Clinical Impact Concomitant use of MAVENCLAD with interferon-beta didnot change the exposure of cladribine to a clinicallysignificant effect; however, lymphopenia risk may beincreased [see Warnings and Precautions (5.3)].
Prevention or Management Concomitant use is not recommended.
7.3 Hematotoxic Drugs
Clinical Impact Concomitant use of MAVENCLAD with hematotoxic drugsmay increase the risk of adverse reactions because of theadditive hematological effects [see Warnings and Precautions(5.5)].
Prevention or Management Monitor hematological parameters.
7.4 Antiviral and Antiretroviral Drugs
Clinical Impact Compounds that require intracellular phosphorylation tobecome active (e.g., lamivudine, zalcitabine, ribavirin,stavudine, and zidovudine) could interfere with theintracellular phosphorylation and activity of cladribine.
Prevention or Management Avoid concomitant use.
7.5 Potent ENT, CNT and BCRP Transporter Inhibitors
Clinical Impact Cladribine is a substrate of breast cancer resistance protein
(BCRP), equilibrative nucleoside (ENT1), and concentrative
nucleoside (CNT3) transport proteins. The bioavailability,
intracellular distribution, and renal elimination of cladribine
may be altered by potent ENT1, CNT3, and BCRP transporter
inhibitors.
Prevention or Management Avoid co-administration of potent ENT1, CNT3, or BCRP
transporter inhibitors (e.g., ritonavir, eltrombopag, curcumin,
cyclosporine, dilazep, nifedipine, nimodipine, cilostazol,
sulindac, dipyridamole, or re |
