Chemical formula: C₂₈H₄₅NO₅S Molecular mass: 507.73 g/mol PubChem compound: 25185057
Lefamulin interacts in the following cases:
Lefamulin should be used with caution in patients with renal failure who require dialysis because metabolic disturbances associated with renal failure may lead to QT prolongation.
Patients with moderate (Child-Pugh Class B) or severe (Child-Pugh Class C) hepatic impairment have reduced lefamulin protein binding compared to healthy subjects or subjects with mild (Child-Pugh Class A) hepatic impairment. Treatment should be initiated in patients with moderate or severe hepatic impairment only after a careful benefit/risk evaluation, due to possible adverse reactions related to higher free concentrations of lefamulin, including prolongation of the QTcF interval. Patients should be monitored closely during treatment.
Use with caution.
Possible mechanism of interaction: inhibition of CYP3A4.
Caution is recommended. Co-administration with lefamulin may lead to higher exposures of metformin. Patients should be monitored.
Possible mechanism of interaction: inhibition of MATE, OCT1, OCT2.
Caution is recommened. when co-administered with oral lefamulin. Consider dosage adjustment of midazolam.
No dose adjustment required when co-administered with intravenous lefamulin.
Possible mechanism of interaction: inhibition of CYP3A4.
Use with caution.
Possible mechanism of interaction: inhibition of CYP3A, BCRP, OATP1.
Monitor for adverse reactions during co-administration with lefamulin. Consider dosage adjustment of zolpidem.
Possible mechanism of interaction: inhibition of CYP3A4.
Lefamulin should be used with caution in patients with mild, moderate, or severe cirrhosis because metabolic disturbances associated with hepatic insufficiency may lead to QT prolongation.
There are no data from the use of lefamulin in pregnant women. Studies in animals have shown increased incidence of stillbirth. Animal studies are insufficient with respect to embryo-foetal development. Lefamulin is not recommended during pregnancy.
It is unknown whether lefamulin/metabolites are excreted in human milk. Available pharmacokinetic data in animals have shown excretion of lefamulin/metabolites in milk. A risk to the newborns/infants cannot be excluded. Breast-feeding should be discontinued during treatment with lefamulin.
Women of childbearing potential should use effective contraception during treatment with lefamulin. Women taking oral contraceptives should use an additional barrier method of contraception.
The effects of lefamulin on fertility in humans have not been studied.
Lefamulin caused no impairment of fertility or reproductive performance in rats.
Lefamulin has no influence on the ability to drive and use machines.
The most frequently reported adverse reactions are administration site reactions (7%), diarrhoea (7%), nausea (4%), vomiting (2%), hepatic enzyme elevation (2%), headache (1%), hypokalaemia (1%), and insomnia (1%).
Administration site reactions apply to intravenous administration and led to treatment discontinuation in <1%. Gastrointestinal disorders were predominantly associated with the oral formulation of lefamulin and led to treatment discontinuation in <1%.
The most frequently reported serious adverse reaction is atrial fibrillation (<1%).
Based on pooled data from Phase 3 trials for both intravenous and oral formulations, the following adverse reactions have been identified with lefamulin. Adverse reactions are classified according to System Organ Class and frequency. Frequency categories are defined as: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), very rare (<1/10,000), and not known (cannot be estimated from the available data).
Frequency of adverse reactions by system organ class from clinical trials:
| System organ class | Common | Uncommon |
|---|---|---|
| Infections and infestations | Clostridioides difficile colitis Oropharyngeal candidiasis Vulvovaginal mycotic infection | |
| Blood and lymphatic system disorders | Anaemia Thrombocytopenia | |
| Metabolism and nutrition disorders | Hypokalaemia | |
| Psychiatric disorders | Insomnia | Anxiety |
| Nervous system disorders | Headache | Dizziness Somnolence |
| Cardiac disorders | Electrocardiogram QT prolonged | Atrial fibrillation Palpitations |
| Respiratory, thoracic and mediastinal disorders | Oropharyngeal pain | |
| Gastrointestinal disorders | Diarrhoea Nausea Vomiting | Abdominal pain Abdominal pain upper Constipation Dyspepsia Epigastric discomfort Gastritis Gastritis erosive |
| Hepatobiliary disorders | Alanine aminotransferase increased* Aspartate aminotransferase increased* | Alkaline phosphatase increased Gamma-glutamyltransferase increased |
| Renal and urinary disorders | Urinary retention | |
| General disorders and administration site conditions | Infusion site pain Infusion site phlebitis Infusion site erythema | Infusion site bruising Infusion site coldness |
| Investigations | Creatinine phosphokinase increased |
* In Phase 3 trials (pooled data for intravenous and oral formulations), post-baseline alanine aminotransferase values >3x and >5x ULN occurred in 5% and 2% of lefamulin patients compared with 5% and 1% of moxifloxacin patients. Post-baseline aspartate aminotransferase values >3x and >5x ULN occurred in 4% and 1% of lefamulin patients compared with 2% and 1% of moxifloxacin patients. Those affected were asymptomatic with reversible clinical laboratory findings that typically peaked within the first week of lefamulin dosing. No lefamulin patient met Hy’s Law criteria.
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