Contraindications
4 CONTRAINDICATIONS • Ocular or periocular infections ( 4.1 ) • Hypersensitivity ( 4.2 ) 4.1 Ocular or Periocular Infections CIMERLI is contraindicated in patients with ocular or periocular infections. 4.2 Hypersensitivity CIMERLI is contraindicated in patients with known hypersensitivity to ranibizumab products or any of the excipients in CIMERLI. Hypersensitivity reactions may manifest as severe intraocular inflammation.
Pregnancy & Breastfeeding
8.1 Pregnancy Risk Summary There are no adequate and well-controlled studies of ranibizumab products administered in pregnant women. Administration of ranibizumab to pregnant monkeys throughout the period of organogenesis resulted in a low incidence of skeletal abnormalities at intravitreal doses 13-times the predicted human exposure (based on maximal serum trough levels [C max ]) after a single eye treatment at the recommended clinical dose. No skeletal abnormalities were observed at serum trough levels equivalent to the predicted human exposure after a single eye treatment at the recommended clinical dose [see Animal Data] . Animal reproduction studies are not always predictive of human response, and it is not known whether ranibizumab products can cause fetal harm when administered to a pregnant woman. Based on the anti-VEGF mechanism of action for ranibizumab products [see Clinical Pharmacology ( 12.1 )] , treatment with ranibizumab products may pose a risk to human embryofetal development. CIMERLI should be given to a pregnant woman only if clearly needed. Data Animal Data An embryo-fetal developmental toxicity study was performed on pregnant cynomolgus monkeys. Pregnant animals received intravitreal injections of ranibizumab every 14 days starting on Day 20 of gestation, until Day 62 at doses of 0, 0.125, and 1 mg/eye. Skeletal abnormalities including incomplete and/or irregular ossification of bones in the skull, vertebral column, and hindlimbs and shortened supernumerary ribs were seen at a low incidence in fetuses from animals treated with 1 mg/eye of ranibizumab. The 1 mg/eye dose resulted in trough serum ranibizumab levels up to 13 times higher than predicted C max levels with single eye treatment in humans. No skeletal abnormalities were seen at the lower dose of 0.125 mg/eye, a dose which resulted in trough exposures equivalent to single eye treatment in humans. No effect on the weight or structure of the placenta, maternal toxicity, or embryotoxicity w