Recarbrio

What Is Recarbrio?

Recarbrio (imipenem, cilastatin, and relebactam) is a combination of a penem antibacterial, a renal dehydropeptidase inhibitor, and a beta¬ lactamase inhibitor, indicated in patients 18 years of age and older who have limited or no alternative treatment options, for the treatment of the following infections caused by susceptible gram-negative bacteria: complicated urinary tract infections, including pyelonephritis (cUTI) and complicated intra-abdominal infections (cIAI).

What Are Side Effects of Recarbrio?

Common side effects of Recarbrio include:

• diarrhea,
• nausea,
• headache,
• vomiting,
• increased alanine aminotransferase,
• increased aspartate aminotransferase,
• infusion site reactions (pain, redness, swelling), fever, and
• high blood pressure (hypertension)

Dosage for Recarbrio

The dose of Recarbrio is 1.25 grams (imipenem 500 mg, cilastatin 500 mg, relebactam 250 mg) administered by intravenous (IV) infusion over 30 minutes every 6 hours in patients 18 years of age and older with creatinine clearance (CLcr) 90 mL/min or greater.

What Drugs, Substances, or Supplements Interact with Recarbrio?

Recarbrio may interact with ganciclovir, valproic acid, or divalproex sodium. Tell your doctor all medications and supplements you use.

Recarbrio During Pregnancy and Breastfeeding

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

Additional Information

Our Recarbrio (imipenem, cilastatin, and relebactam) 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.

 

Recarbrio Consumer Information

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

• tremors;
• a seizure; or
• severe stomach pain, diarrhea that is watery or bloody (even if it occurs months after your last dose).

Common side effects may include:

• increased blood pressure;
• nausea, diarrhea, vomiting;
• abnormal liver function tests;
• fever;
• headache; or
• pain, bruising, swelling, or irritation where the medicine was injected.

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.

Read the entire detailed patient monograph for Recarbrio (Imipenem, Cilastatin, and Relebactam for Injection)

 

Recarbrio Professional Information

SIDE EFFECTS

The following serious adverse reactions are described in greater detail in the Warnings and Precautions section.

• Hypersensitivity Reactions [see WARNINGS AND PRECAUTIONS]
• Seizures and Other Central Nervous System Adverse Reactions [see WARNINGS AND PRECAUTIONS]
• Increased Seizure Potential Due to Interaction with Valproic Acid [see WARNINGS AND PRECAUTIONS]
• Clostridioides difficile-Associated Diarrhea (CDAD) [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 a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Overview Of The Safety Evaluation Of RECARBRIO

Safety was primarily evaluated in three active-controlled, double-blind trials in HABP/VABP, cUTI, and cIAI (Trials 1, 2, and 3 respectively).

In the HABP/VABP trial (Trial 1), patients were treated with either RECARBRIO or piperacillin and tazobactam (4.5 grams).

In the cUTI trial (Trial 2) and cIAI trial (Trial 3), patients in the treatment arms were treated with either imipenem 500 mg/cilastatin 500 mg and relebactam 250 mg or imipenem 500 mg/cilastatin 500 mg and relebactam 125 mg (not an approved dose), and patients in the control arm were treated with imipenem 500 mg/cilastatin 500 mg plus placebo (IV normal saline). Across Trials 2 and 3, the mean duration of IV therapy in patients treated with imipenem/cilastatin plus relebactam 250 mg was approximately 7 days.

Clinical Trial Experience In Patients With HABP/VABP

Trial 1 included 266 adult patients treated with RECARBRIO and 269 patients treated with piperacillin and tazobactam (4.5 grams) administered intravenously over 30 minutes every 6 hours. The mean age was 60 years, 43 % of patients were 65 years of age and older, 31 % were female and 22 % had polymicrobial infection. The mean Acute Physiology and Chronic Health Evaluation (APACHE) II score was 15 and 48 % of patients had an APACHE II score greater than or equal to 15 at baseline. Overall, 260 (49 %) patients were ventilated at enrollment, including 194 (36 %) patients with VABP and 66 (12 %) patients with ventilated HABP.

Clinical Trial Experience In Patients With cUTI Including Pyelonephritis

Trial 2 included 198 adult patients treated with imipenem/cilastatin and relebactam (99 patients each with imipenem 500 mg/cilastatin 500 mg plus relebactam 125 mg or relebactam 250 mg) and 100 patients treated with imipenem 500 mg/cilastatin 500 mg, administered intravenously over 30 minutes every 6 hours. After a minimum of 4 days of IV therapy, patients could be switched to oral ciprofloxacin (500 mg daily every 12 hours) to complete the treatment course of 4 to 14 days total (IV plus oral), at the discretion of the investigator. The mean age was 56 years, 40 % of patients were 65 years of age and older, 16 % were 75 years of age and older, 50 % were female, and approximately 18 % had moderate to severe renal impairment.

Clinical Trial Experience In Patients With cIAI

Trial 3 included 233 adult patients treated with imipenem/cilastatin plus relebactam (116 subjects with imipenem 500 mg/cilastatin 500 mg and relebactam 125 mg and 117 subjects with imipenem 500 mg/cilastatin 500 mg plus relebactam 250 mg), and 114 patients treated with imipenem 500 mg/cilastatin 500 mg, administered intravenously over 30 minutes every 6 hours for 4 to 14 days, at the discretion of the investigator. The mean age was 49 years, 23 % of the patients were 65 years of age and older, 9.8 % were 75 years of age and older, and 42 % were female.

Serious Adverse Reactions And Adverse Reactions Leading To Discontinuation

In Trial 1, serious adverse reactions occurred in 27 % (71/266) of patients receiving RECARBRIO and 32 % (86/269) of patients receiving piperacillin and tazobactam. Adverse reactions leading to death were reported in 15 % (40/266) of patients receiving RECARBRIO and 21 % (57/269) of patients receiving piperacillin and tazobactam.

Adverse reactions leading to discontinuation occurred in 5.6 % (15/266) of patients receiving imipenem 500 mg/cilastatin 500 mg/ relebactam 250 mg and 8.2 % (22/269) of patients receiving piperacillin and tazobactam.

In Trials 2 and 3, serious adverse reactions occurred in 3.2 % (7/216) of patients receiving imipenem 500 mg/cilastatin 500 mg plus relebactam 250 mg and 5.1 % (11/214) of patients receiving imipenem 500 mg/cilastatin 500 mg. There were no deaths reported in patients receiving imipenem 500 mg/cilastatin 500 mg plus relebactam 250 mg or imipenem 500 mg/cilastatin 500 mg alone. Deaths were reported in 1.4 % (3/215) of patients receiving imipenem 500 mg/cilastatin 500 mg plus relebactam 125 mg (not an approved dose).

Adverse reactions leading to discontinuation occurred in 1.9 % (4/216) of patients receiving imipenem 500 mg/cilastatin 500 mg plus relebactam 250 mg and 2.3 % (5/214) of patients receiving imipenem 500 mg/cilastatin 500 mg.

Common Adverse Reactions

In Trial 1, adverse reactions occurred during the protocol-specified follow-up period, which was IV therapy plus 14 days following completion of therapy, in 85 % (226/266) of patients receiving RECARBRIO and 87 % (233/269) of patients receiving piperacillin and tazobactam. Table 3 lists the most common adverse reactions occurring in ≥ 4 % of patients receiving imipenem 500 mg/cilastatin 500 mg/relebactam 250 mg or piperacillin and tazobactam in Trial 1.

Table 3: Adverse Reactions Occurring in Greater Than or Equal to 4 % of HABP/VABP Patients Receiving RECARBRIO in Trial 1

Adverse Reaction	RECARBRIOa (N=266) N (%)	Piperacillin/Tazobactamb (N=269) N (%)
Blood and lymphatic system disorders
Anemia	28 (10.5%)	27 (10.0%)
Gastrointestinal disorders
Constipation	11 (4.1%)	3 (1.1%)
Diarrhea	21 (7.9%)	30 (11.2%)
General disorders and administration site conditions
Pyrexia	11 (4.1%)	20 (7.4%)
Laboratory investigations
Alanine aminotransferase increased	26 (9.8%)	19 (7.1%)
Aspartate aminotransferase increased	31 (11.7%)	20 (7.4%)
Metabolism and nutrition disorders
Hypokalemiac	21 (7.9%)	26 (9.7%)
Hyponatremiad	17 (6.4%)	3 (1.1%)
Skin and subcutaneous tissue disorders
Rashe	11 (4.1%)	5 (1.9%)
aRECARBRIO, IV every 6 hours. bPiperacillin 4000 mg and Tazobactam 500 mg (4.5 grams), IV every 6 hours. cHypokalemia includes hypokalemia and blood potassium decreased. dHyponatremia includes hyponatremia and blood sodium decreased. eRash includes rash, rash erythematous, and rash generalized.

Less Common Adverse Reactions Reported In Trial 1

The following selected adverse reaction was reported in RECARBIO-treated subjects at a rate of less than 4 %:

Blood and lymphatic system disorders: thrombocytopenia

In Trials 2 and 3, adverse reactions occurred during the protocol-specified follow-up period, which was IV therapy plus 14 days following completion of therapy, in 39 % (85/216) of patients receiving imipenem 500 mg/cilastatin 500 mg plus relebactam 250 mg and 36 % (77/214) of patients receiving imipenem 500 mg/cilastatin 500 mg. Table 4 lists the most common adverse reactions occurring in ≥ 1 % of patients receiving imipenem 500 mg/cilastatin 500 mg plus relebactam 250 mg or imipenem 500 mg/cilastatin 500 mg in Trials 2 and 3.

Table 4: Adverse Reactions Occurring in Greater Than or Equal to 1 % of cUTI and cIAI Patients Receiving Imipenem/Cilastatin plus Relebactam 250 mg or Imipenem/Cilastatin in Trials 2 and 3

Adverse Reaction	Imipenem/Cilastatin and Relebactam 250 mga (N=216) N (%)	IMI + Placebob (N=214) N (%)
Blood and lymphatic system disorders
Anemiac	2 (1%)	4 (2%)
Gastrointestinal disorders
Diarrhea	12 (6%)	9 (4%)
Nausea	12 (6%)	12 (6%)
Vomiting	7 (3%)	4 (2%)
General disorders and administration site conditions
Phlebitis/Infusion site reactionsd	5 (2%)	3 (1%)
Pyrexia	5 (2%)	3 (1%)
Laboratory Investigations
Alanine aminotransferase increased	7 (3%)	4 (2%)
Aspartate aminotransferase increased	6 (3%)	3 (1%)
Lipase increased	3 (1%)	4 (2%)
Blood creatinine increased	1 (<1%)	3 (1%)
Nervous system disorders
Headache	9 (4%)	5 (2%)
Central nervous system adverse reactionse	2 (1%)	5 (2%)
Vascular disorders
Hypertensionf	4 (2%)	6 (3%)
aImipenem/Cilastatin (500 mg/500 mg) + Relebactam (250 mg), IV every 6 hours. bImipenem/Cilastatin (500 mg/500 mg) + Placebo, IV every 6 hours. cAnemia includes anemia and hemoglobin decreased. dInfusion site reactions include infusion site phlebitis, infusion site erythema, and infusion site pain. eCentral nervous system adverse reactions include agitation, apathy, confusional states, delirium, disorientation, slow speech, and somnolence. fHypertension includes hypertension and blood pressure increased.

Other Adverse Reactions Associated With Imipenem/Cilastatin

Adverse reactions reported with imipenem/cilastatin (a component of RECARBRIO) in clinical studies or during post-marketing experience are listed below. These adverse reactions are not listed above for patients treated with RECARBRIO in Trial 1 or imipenem 500 mg/cilastatin 500 mg plus relebactam 250 mg in Trials 2 and 3.

Blood and Lymphatic System Disorders: agranulocytosis, increased eosinophils, hemolytic anemia

Nervous System Disorders: seizure

Hepatobiliary Disorders: hepatic failure, jaundice

Laboratory Investigations: blood lactate dehydrogenase increased, coombs test positive, eosinophil count increased

Read the entire FDA prescribing information for Recarbrio (Imipenem, Cilastatin, and Relebactam for Injection)