ave a positive purified protein derivative (PPD) testresult [see Dosage and Administration (2.2)].
Administer prophylaxis for Herpes Zoster, Pneumocystis jirovecii, and fungal infection tomitigate the risk to patients while receiving GAMIFANT. Employ surveillance testing duringtreatment with GAMIFANT.
Closely monitor patients receiving GAMIFANT for signs or symptoms of infection, promptlyinitiate a complete diagnostic workup appropriate for an immunocompromised patient, andinitiate appropriate antimicrobial therapy.
5.2 Increased Risk of Infection with Use of Live Vaccines
Do not administer live or live attenuated vaccines to patients receiving GAMIFANT and for atleast 4 weeks after the last dose of GAMIFANT. The safety of immunization with live vaccinesduring or following GAMIFANT therapy has not been studied.
5.3 Infusion-Related Reactions
Infusion-related reactions including drug eruption, pyrexia, rash, erythema, and hyperhidrosiswere reported with GAMIFANT treatment in 27% of patients. In one-third of these patients, theinfusion-related reaction occurred during the first infusion.
All infusion related reactions were reported as mild to moderate. Monitor patients for infusionrelatedreactions. Interrupt infusion for infusion reactions and institute appropriate medicalmanagement prior to continuing infusion at a slower rate.
6 ADVERSE REACTIONS
The following adverse reactions are described elsewhere in the labeling:
Infections [see Warnings and Precautions (5.1)]
Infusion-Related Reactions [see Warnings and Precautions (5.3)]
6.1 Clinical Trial Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction ratesobserved in the clinical trials of a drug cannot be directly compared to rates in the clinical trialsof another drug and may not reflect the rates observed in practice.
The safety data described in this section reflect exposure to GAMIFANT in which 34 patientswith untreated primary HLH and previously treated patients with primary HLH (NCT01818492)received GAMIFANT at a starting dose of 1 mg/kg every 3 days with dose increases up to 10 mg/kg [see Dosage and Administration (2.1) and Clinical Studies (14)]. The median duration oftreatment with GAMIFANT was 59 days (range: 4 to 245 days) and the median cumulative dosewas 25 mg/kg (range: 4 to 254 mg/kg).
The median age of study population was 1 year (range: 0.1 to 13 years), 53% were female, and65% were Caucasian.
Serious adverse reactions were reported in 53% of patients. The most common serious adversereactions (≥ 3%) included infections, gastrointestinal hemorrhage, and multiple organdysfunction. Fatal adverse reactions occurred in two (6%) of patients and included septic shockand gastrointestinal hemorrhage.
Disseminated histoplasmosis led to drug discontinuation in one patient. The most commonlyreported adverse reactions (≥ 20%) were infections, hypertension, infusion-related reactions, andpyrexia. Adverse reactions reported in ≥ 10% of patients during treatment with GAMIFANT are
presented in Table 2.
Table 2: Adverse Reactions Reported in ≥ 10% of Patients with Primary HLHAdverse Reactions GAMIFANT
(%)
(N = 34)
Infectionsa 56
Hypertensionb 41
Infusion-related reactionsc 27
Pyrexia 24
Hypokalemia 15
Constipation 15
Rash 12
Abdominal pain 12
Cytomegalovirus infection 12
Diarrhea 12
Lymphocytosis 12
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