pombiliti

Important safety information

Embryo-Fetal Toxicity: May cause embryo-fetal harm. Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception during treatment and for at least 60 days after the last dose. ( 4 , 5.4 , 8.1 , 8.3 ) Risks Associated with Opfolda: Refer to the Opfolda Prescribing Information for a description of additional risks for Opfolda. ( 5.5 ) 5.1 Hypersensitivity Reactions Including Anaphylaxis Life-threatening hypersensitivity reactions, including anaphylaxis, have been reported in POMBILITI-treated patients. In clinical trials, 43 (27%) POMBILITI-treated patients experienced hypersensitivity reactions, including 4 (3%) patients who reported severe hypersensitivity reactions and 4 (3%) additional patients who experienced anaphylaxis (fulfilling at least one of the Sampson criteria). Three of the 4 (2%) patients experiencing anaphylaxis discontinued from the trial [see Clinical Studies (14) ] . Two of the 4 patients who experienced anaphylaxis developed high anti-cipaglucosidase alfa-atga antibody titers [see Clinical Pharmacology (12.6) ] . Anaphylaxis signs and symptoms included dyspnea, rash, hypotension, bronchospasm, edema, pharyngeal edema, and tongue swelling. Symptoms of severe hypersensitivity reactions included urticaria, pruritus, and flushing. Prior to POMBILITI administration, consider pretreating with antihistamines, antipyretics, and/or corticosteroids. Appropriate medical support measures, including cardiopulmonary resuscitation equipment, should be readily available during POMBILITI administration. If a severe hypersensitivity reaction (e.g., anaphylaxis) occurs, POMBILITI should be discontinued immediately, and appropriate medical treatment should be initiated. The risks and benefits of readministering POMBILITI following severe hypersensitivity reaction (including anaphylaxis) should be considered. Patients may be rechallenged using slower infusion rates. In patients with severe hypersensitivity reaction, desensitization measures to POMBILITI may be considered. If the decision is made to readminister POMBILITI, ensure the patient tolerates the infusion. If the patient tolerates the infusion, the dosage (dose and/or the rate) may be increased to reach the approved recommended dosage. If a mild or moderate hypersensitivity reaction occurs, the infusion rate may be slowed or temporarily stopped [see Dosage and Administration (2.3) ]. 5.2 Infusion-Associated Reactions In clinical trials, IARs were reported to occur at any time during and/or within a few hours after the POMBILITI infusion and were more likely to occur with higher infusion rates. IARs were reported in 48 (32%) POMBILITI-treated patients in clinical trials. In these trials, 4 (3%) POMBILITI-treated patients reported 11 severe IARs including symptoms of pharyngeal edema, anaphylactic reaction, urticaria, pruritus, chills, dyspnea, and flushing. The majority of IARs were assessed as mild to moderate. IARs that led to treatment discontinuation were urticaria, anaphylactic reaction, chills, and hypotension. Antihistamines, antipyretics, and/or corticosteroids can be given prior to POMBILITI administration to reduce the risk of infusion-associated reactions (IARs). However, IARs may still occur in patients after receiving pretreatment. If severe IARs occur, immediately discontinue the POMBILITI infusion, initiate appropriate medical treatment, and assess the benefits and risks of readministering POMBILITI following severe IARs. Patients may be rechallenged using slower infusion rates. Once a patient tolerates the infusion, the infusion rate may be increased to reach the recommended infusion rate. If mild or moderate IARs occur regardless of pretreatment, decreasing the infusion rate or temporarily stopping the infusion may ameliorate the symptoms [see Dosage and Administration (2.3) ]. Patients with an acute underlying illness at the time of POMBILITI infusion may be at greater risk for IARs. Patients with advanced Pompe disease may have compromised cardiac and respiratory function, which may predispose them to a higher risk of severe complications from IARs. 5.3 Risk of Acute Cardiorespiratory Failure in Susceptible Patients Patients susceptible to fluid volume overload, or those with acute underlying respiratory illness or compromised cardiac or respiratory function for whom fluid restriction is indicated may be at risk of serious exacerbation of their cardiac or respiratory status during the POMBILITI infusion. More frequent monitoring of vitals should be performed during POMBILITI infusion in these patients. Some patients may require prolonged observation times. 5.4 Embryo-Fetal Toxicity Based on findings from animal reproduction studies, POMBILITI in combination with Opfolda may cause embryo-fetal harm when administered to a pregnant female and is contraindicated during pregnancy. In a rabbit embryo-fetal development study, great vessel and cardiac malformations were increased in offspring of pregnant rabbits treated with cipaglucosidase alfa‑atga in combination with oral miglustat at 16‑fold and 3‑fold, respectively, the maximum recommended human dose (MRHD) based on plasma area under the plasma concentration-time curve (AUC) exposure. Verify the pregnancy status in females of reproductive potential prior to initiating treatment with POMBILITI in combination with Opfolda. Advise females of reproductive potential to use effective contraception during treatment with POMBILITI in combination with Opfolda and for at least 60 days after the last dose [see Use in Specific Populations (8.1 , 8.3 )]. 5.5 Risks Associated with Opfolda POMBILITI must be administered in combination with Opfolda. Refer to the Opfolda Prescribing Information for a description of additional risks for Opfolda including, but not limited to, the warnings and precautions for Opfolda.