Kimyrsa

Kimyrsa Side Effects Center

What Is Kimyrsa?

Kimyrsa (oritavancin) is a lipoglycopeptide antibacterial drug used to treat adult patients with acute bacterial skin and skin structure infections caused or suspected to be caused by susceptible isolates of designated Gram-positive microorganisms.

What Are Side Effects of Kimyrsa?

Side effects of Kimyrsa include:

• headache,
• nausea,
• vomiting,
• limb and subcutaneous abscesses,
• diarrhea
,
• hypersensitivity,
• itching,
• chills,
• fever,
• dizziness,
• infusion site phlebitis,
• infusion site reaction,
• increased alanine aminotransferase,
• increased aspartate aminotransferase, and
• fast heart rate

Dosage for Kimyrsa

The recommended dosage of Kimyrsa is 1,200 mg administered as a single dose by intravenous infusion over 1 hour in patients 18 years and older.

Kimyrsa In Children

Safety and effectiveness of Kimyrsa in pediatric patients (younger than 18 years of age) have not been established.

What Drugs, Substances, or Supplements Interact with Kimyrsa?

Kimyrsa may interact with other medicines such as:

• CYP substrates

Tell your doctor all medications and supplements you use.

Kimyrsa During Pregnancy and Breastfeeding

Tell your doctor if you are pregnant or plan to become pregnant before using Kimyrsa; it is unknown how it would affect a fetus. It is unknown if Kimyrsa passes into breast milk or how it could affect a nursing infant. Consult your doctor before breastfeeding.

Additional Information

Our Kimyrsa (oritavancin) for Injection, for Intravenous Use Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

 

Kimyrsa Professional Information

SIDE EFFECTS

The following adverse reactions are also discussed in the Warnings and Precautions section of labeling:

• Hypersensitivity Reactions [see WARNINGS AND PRECAUTIONS]
• Infusion Related Reactions [see WARNINGS AND PRECAUTIONS]
• Clostridioides difficile-associated Diarrhea [see WARNINGS AND PRECAUTIONS]
• Osteomyelitis [see WARNINGS AND PRECAUTIONS]

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of oritavancin products cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The safety of KIMYRSA has been established from adequate and well-controlled trials of another oritavancin product, ORBACTIV (hereinafter referred to as oritavancin), in patients with ABSSSI, and a study of KIMYRSA in patients with ABSSSI.

Oritavancin has been evaluated in two, double-blind, controlled ABSSSI clinical trials, which included 976 adult patients treated with a single 1,200 mg intravenous dose of oritavancin and 983 patients treated with intravenous vancomycin for 7 to 10 days. The median age of patients treated with oritavancin was 45.6 years, ranging between 18 and 89 years of age with 8.8% ≥65 years of age. Patients treated with oritavancin were predominantly male (65.4%), 64.4% were Caucasian, 5.8% were African American, and 28.1% were Asian. Safety was evaluated for up to 60 days after dosing.

In the pooled ABSSSI clinical trials, serious adverse reactions were reported in 57/976 (5.8%) patients treated with oritavancin and 58/983 (5.9%) treated with vancomycin. The most commonly reported serious adverse reaction was cellulitis in both treatment groups: 11/976 (1.1%) in oritavancin and 12/983 (1.2%) in the vancomycin arms, respectively.

The most commonly reported adverse reactions (≥3%) in patients receiving a single 1,200 mg dose of oritavancin in the pooled ABSSSI clinical trials were: headache, nausea, vomiting, limb and subcutaneous abscesses, and diarrhea.

In the pooled ABSSSI clinical trials, oritavancin was discontinued due to adverse reactions in 36/976 (3.7%) of patients; the most common reported reactions leading to discontinuation were cellulitis (4/976, 0.4%) and osteomyelitis (3/976, 0.3%).

Table 1 provides selected adverse reactions occurring in ≥1.5% of patients receiving oritavancin in the pooled ABSSSI clinical trials. There were 540 (55.3%) patients in the oritavancin arm and 559 (56.9%) patients in the vancomycin arm, who reported ≥1 adverse reaction.

Table 1: Incidence of Selected Adverse Reactions Occurring in ≥1.5% of Patients Receiving Oritavancin in the Pooled ABSSSI Clinical Trials

Adverse Reactions	Oritavancin N=976 (%)	Vancomycin N=983 (%)
Gastrointestinal disorders
Diarrhea	36 (3.7)	32 (3.4)
Nausea	97 (9.9)	103 (10.5)
Vomiting	45 (4.6)	46 (4.7)
Nervous system disorders
Dizziness	26 (2.7)	26 (2.6)
Headache	69 (7.1)	66 (6.7)
General disorders and administration
Infusion site phlebitis	24 (2.5)	15 (1.5)
Infusion site reaction	19 (1.9)	34 (3.5)
Infections and infestations
Abscess (limb and subcutaneous)	37 (3.8)	23 (2.3)
Investigations
Alanine aminotransferase increased	27 (2.8)	15 (1.5)
Aspartate aminotransferase increased	18 (1.8)	15 (1.5)
Cardiac disorders
Tachycardia	24 (2.5)	11 (1.1)

The following selected adverse reactions were reported in oritavancin-treated patients at a rate of less than 1.5%:

Blood and lymphatic system disorders: anemia, eosinophilia

General disorders and administration site conditions: infusion site erythema, extravasation, induration, pruritus, rash, edema peripheral

Immune system disorders: hypersensitivity

Infections and infestations: osteomyelitis

Investigations: total bilirubin increased, hyperuricemia

Metabolism and nutrition disorders: hypoglycemia

Musculoskeletal and connective tissue disorders: tenosynovitis, myalgia

Respiratory, thoracic and mediastinal disorders: bronchospasm, wheezing

Skin and subcutaneous tissue disorders: urticaria, angioedema, erythema multiforme, pruritus, leucocytoclastic vasculitis, rash.

KIMYRSA has been evaluated in a randomized, open-label, multi-center ABSSSI study which included 50 adult patients treated with a single 1,200 mg intravenous dose of KIMYRSA administered by intravenous infusion over 1 hour, and 52 patients treated with a single 1,200 mg intravenous dose of oritavancin administered by intravenous infusion over 3 hours.

Selected adverse reactions occurring in ≥2 patients receiving either KIMYRSA or oritavancin in the open-label, multi-center ABSSSI study were diarrhea, nausea, vomiting, hypersensitivity, pruritus, chills, headache and pyrexia.

Immunogenicity

There is potential for immunogenicity following administration of oritavancin products, including KIMYRSA. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Because several factors in an assay may influence the observed incidence of antibody positivity, comparison of the incidence of antibodies to oritavancin in the studies described below with the incidence of antibodies in other studies or to other products may be misleading.

Positive indirect and direct antiglobulin tests (IAT/DAT) were noted with the administration of KIMYRSA and oritavancin in studies with healthy subjects and patients with ABSSSI. In the randomized, open-label, multi-center ABSSSI study, positive antiglobulin tests were reported in 9.6% (5/52) of subjects who received oritavancin and 2% (1/50) of subjects who received KIMYRSA. Oritavancin-dependent RBC antibodies were detected when tested in the presence of drug for three subjects in the oritavancin group. In a healthy volunteer study, 66% (22/32) subjects receiving KIMYRSA had a positive IAT 15 days after receiving dosing and one subject had a positive DAT at 8 days after dosing.

There were no reports of hemolysis in subjects who had positive IAT/DAT. If hemolytic anemia develops following treatment with KIMYRSA provide appropriate care. Positive IAT may interfere with cross-matching before blood transfusion [see DRUG INTERACTIONS].

DRUG INTERACTIONS

Effect Of KIMYRSA On CYP Substrates

A screening drug-drug interaction study indicated that oritavancin is a nonspecific, weak inhibitor (CYP2C9 and CYP2C19) or inducer (CYP3A4 and CYP2D6) of several CYP isoforms [see CLINICAL PHARMACOLOGY]. A drug-drug interaction study that assessed the interaction potential of a single 1,200 mg dose of oritavancin on the pharmacokinetics of S-warfarin (CYP2C9 probe substrate) showed no effect of oritavancin on S-warfarin Cmax or AUC.

Avoid administering KIMYRSA concomitantly with drugs that are predominantly metabolized by one of the affected CYP450 enzymes, as co-administration may increase or decrease concentrations of those drugs. Patients should be closely monitored for signs of toxicity or lack of efficacy if they have been given KIMYRSA while on a potentially affected compound (e.g. patients should be monitored for bleeding if concomitantly receiving KIMYRSA and warfarin).

Drug-Laboratory Test Interactions

Prolongation Of Certain Laboratory Coagulation Tests

KIMYRSA may artificially prolong certain laboratory coagulation tests (see Table 2) by binding to and preventing the action of the phospholipid reagents which activate coagulation in commonly used laboratory coagulation tests [see CONTRAINDICATIONS and WARNINGS AND PRECAUTIONS]. For patients who require monitoring of anticoagulation effect within the indicated time after KIMYRSA dosing, a non-phospholipid dependent coagulation test such as a Factor Xa (chromogenic) assay or an alternative anticoagulant not requiring aPTT monitoring may be considered.

Oritavancin does not interfere with coagulation in vivo. In addition, oritavancin does not affect tests that are used for diagnosis of Heparin Induced Thrombocytopenia (HIT).

Table 2: Coagulation Tests Affected and Unaffected by Oritavancin

Elevated by Oritavancin	Unaffected by Oritavancin
Prothrombin time (PT) up to 12 hours	Chromogenic Factor Xa Assay
International normalized ratio (INR) up to 12 hours	Thrombin Time (TT)
Activated partial thromboplastin time (aPTT) up to 120 hours
Activated clotting time (ACT) up to 24 hours
Silica clot time (SCT) up to 18 hours
Dilute Russell’s viper venom time (DRVVT) up to 72 hours
D-dimer up to 72 hours

Positive Indirect And Direct Antiglobulin Tests (IAT/DAT)

Positive IAT/DAT were noted with administration of oritavancin products, including KIMYRSA, in studies with healthy volunteers and patients with ABSSSI. Positive IAT may interfere with cross-matching before blood transfusion [see ADVERSE REACTIONS].

Read the entire FDA prescribing information for Kimyrsa (Oritavancin for Injeciton)