LEQVIO (inclisiran)

There are 0 contraindications.

There are 1 severe contraindications. Adequate patient monitoring is recommended for safer drug use.

Severe List
Pregnancy

There are 3 moderate contraindications. Clinically significant contraindication, where the condition can be managed or treated before the drug may be given safely.

Moderate List
Chronic kidney disease stage 4 (severe) GFR 15-29 ml/min
Chronic kidney disease stage 5 (failure) GFr<15 ml/min
Severe hepatic disease

There are 1 severe adverse reactions.

More Frequent	Less Frequent
None.	Angioedema

Rare/Very Rare
None.

There are 9 less severe adverse reactions.

More Frequent	Less Frequent
Arthralgia Bronchitis Diarrhea Dyspnea Injection site sequelae Pain in extremities Urinary tract infection	Skin rash Urticaria

Rare/Very Rare
None.

There are no available data on the use of inclisiran in pregnant women to assess drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. However, based on the mechanism of action of inclisiran, the drug may cause fetal harm when administered to pregnant women. Inclisiran increases low-density lipoprotein cholesterol (LDL-C) uptake and lowers its levels in the circulation, thus decreasing cholesterol and possibly other biologically active substances derived from cholesterol.

Discontinue inclisiran when pregnancy is recognized. Alternatively, consider the ongoing therapeutic needs of the individual patient. Treatment of hyperlipidemia is not generally necessary during pregnancy and discontinuation of lipid-lowering agents during pregnancy should have little impact on long-term therapy outcomes for most patients with primary hyperlipidemia.

In animal reproduction studies, no evidence of embryo-fetal toxicity or teratogenicity was observed in rats and rabbits with subcutaneous administration of inclisiran during organogenesis at doses <=5-10 times the maximum recommended human dose (MRHD). Inclisiran crosses the placenta and was detected in rat fetal plasma at concentrations that were 65-154 times lower than maternal levels. No adverse developmental outcomes were observed in offspring of rats administered inclisiran (doses <=5 times the MRHD based on body surface area comparison) from organogenesis through lactation; there was also no evidence of maternal toxicity.

It is not known whether inclisiran is distributed into human milk; the effects of the drug on breast-fed infants or on milk production are also unknown. Inclisiran was detected in the milk of lactating rats in all dose groups; therefore, it is likely that the drug will be present in human milk. Since oligonucleotide-based products typically have poor oral bioavailability; low levels of inclisiran present in breast milk are unlikely to adversely impact an infant's development. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for inclisiran and any potential adverse effects on the breast-fed infant from the drug or from the underlying maternal condition.

In clinical studies, no overall differences in safety or efficacy of inclisiran were observed between patients >=65 years of age and younger patients; however, greater sensitivity to adverse reactions of some older individuals cannot be ruled out.