Applies to cilastatin / imipenem / relebactam: intravenous powder for solution.

Serious side effects

Along with its needed effects, cilastatin/imipenem/relebactam may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor or nurse immediately if any of the following side effects occur while taking cilastatin / imipenem / relebactam:

More common

• Confusion
• decreased urine output
• diarrhea
• dizziness
• dry mouth
• fast or irregular heartbeat
• headache
• increased thirst
• loss of appetite
• mood changes
• muscle pain or cramps
• nausea or vomiting
• numbness or tingling in the hands, feet, or lips
• pale skin
• seizures
• swelling of the face, ankles, or hands
• troubled breathing
• unusual bleeding or bruising
• unusual tiredness or weakness

Less common

• Agitation
• black, tarry stools
• bleeding gums
• blood in the urine or stools
• blurred vision
• fever
• hallucinations
• lack of feeling or emotion
• nervousness
• pain, redness, or swelling at the injection site
• pinpoint red spots on the skin
• pounding in the ears
• sleepiness or unusual drowsiness
• slow heartbeat
• slow speech
• unusual excitement, nervousness, or restlessness

Incidence not known

• Back or leg pains
• chest pain or tightness
• chills
• clay-colored stools
• cough or hoarseness
• dark urine
• difficulty swallowing
• general body swelling
• hives, itching, or skin rash
• light-colored stools
• lower back or side pain
• nosebleeds
• painful or difficult urination
• puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
• reddening of the skin, especially around the ears
• sores, ulcers, or white spots on the lips or in the mouth
• sore throat
• stomach cramps, pain, and tenderness
• swollen glands
• unpleasant breath odor
• vomiting of blood
• watery and severe diarrhea, which may also be bloody
• yellow eyes or skin

Other side effects

Some side effects of cilastatin / imipenem / relebactam may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects.

Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

Less common

• Constipation

For Healthcare Professionals

Applies to cilastatin / imipenem / relebactam: intravenous powder for injection.

Hepatic

Very common (10% or more): Increased AST (up to 11.7%)

Common (1% to 10%): Increased ALT

Imipenem-cilastatin:

-Common (1% to 10%): Increased ALT, increased AST

-Uncommon (0.1% to 1%): Increased serum bilirubin

-Rare (0.01% to 0.1%): Hepatic failure, hepatitis

-Very rare (less than 0.01%): Fulminant hepatitis

-Frequency not reported: Jaundice^[Ref]

Hematologic

Very common (10% or more): Anemia (included anemia, decreased hemoglobin; up to 10.5%)

Frequency not reported: Thrombocytopenia

Imipenem-cilastatin:

-Common (1% to 10%): Anemia, eosinophilia

-Uncommon (0.1% to 1%): Pancytopenia, neutropenia, leukopenia, thrombocytopenia, thrombocytosis, positive Coombs test, prolonged prothrombin time, decreased hemoglobin

-Rare (0.01% to 0.1%): Agranulocytosis

-Very rare (less than 0.01%): Hemolytic anemia, bone marrow depression

-Frequency not reported: Increased eosinophils, increased eosinophil count^[Ref]

Metabolic

Common (1% to 10%): Hypokalemia (included hypokalemia, decreased blood potassium), hyponatremia (included hyponatremia, decreased blood sodium)

Gastrointestinal

Common (1% to 10%): Diarrhea, nausea, vomiting, increased lipase, constipation

Frequency not reported: Clostridioides difficile-associated diarrhea

Imipenem-cilastatin:

-Common (1% to 10%): Nausea, diarrhea, vomiting, increased lipase

-Rare (0.01% to 0.1%): Pseudomembranous colitis, staining of teeth and/or tongue

-Very rare (less than 0.01%): Gastroenteritis, hemorrhagic colitis, abdominal pain, heartburn, glossitis, tongue papilla hypertrophy, increased salivation^[Ref]

Dermatologic

Common (1% to 10%): Rash (included rash, erythematous rash, generalized rash)

Imipenem-cilastatin:

-Common (1% to 10%): Rash (e.g., exanthematous)

-Uncommon (0.1% to 1%): Urticaria, pruritus

-Rare (0.01% to 0.1%): Toxic epidermal necrolysis, angioedema, Stevens-Johnson syndrome, erythema multiforme, exfoliative dermatitis

-Very rare (less than 0.01%): Hyperhidrosis, skin texture changes^[Ref]

Other

Common (1% to 10%): Pyrexia

Imipenem-cilastatin:

-Common (1% to 10%): Pyrexia, increased serum alkaline phosphatase

-Rare (0.01% to 0.1%): Candidiasis

-Very rare (less than 0.01%): Chest discomfort, asthenia/weakness

-Frequency not reported: Increased blood lactate dehydrogenase^[Ref]

Nervous system

Common (1% to 10%): Headache

Uncommon (0.1% to 1%): Central nervous system (CNS) adverse reactions (included agitation, apathy, confusional states, delirium, disorientation, slow speech, somnolence)

Imipenem-cilastatin:

-Common (1% to 10%): Headache, CNS adverse reactions

-Uncommon (0.1% to 1%): Seizures, myoclonic activity, dizziness, somnolence

-Rare (0.01% to 0.1%): Encephalopathy, paresthesia, focal tremor, taste perversion, hearing loss

-Very rare (less than 0.01%): Aggravation of myasthenia gravis, vertigo, tinnitus

-Frequency not reported: Dyskinesia^[Ref]

Local

Common (1% to 10%): Phlebitis/infusion site reactions (included infusion site phlebitis, infusion site erythema, infusion site pain)

Imipenem-cilastatin:

-Common (1% to 10%): Phlebitis/infusion site reactions

-Uncommon (0.1% to 1%): Local pain and induration at injection site^[Ref]

Cardiovascular

Common (1% to 10%): Hypertension (included hypertension, increased blood pressure)

Imipenem-cilastatin:

-Common (1% to 10%): Hypertension, thrombophlebitis

-Uncommon (0.1% to 1%): Hypotension

-Very rare (less than 0.01%): Cyanosis, tachycardia, palpitations, flushing^[Ref]

Renal

Uncommon (0.1% to 1%): Increased blood creatinine, decreased creatinine renal clearance

Imipenem-cilastatin:

-Common (1% to 10%): Increased blood creatinine

-Uncommon (0.1% to 1%): Increased blood urea nitrogen

-Rare (0.01% to 0.1%): Acute renal failure^[Ref]

Psychiatric

Imipenem-cilastatin:

-Uncommon (0.1% to 1%): Hallucinations, confusional states

-Frequency not reported: Agitation^[Ref]

Hypersensitivity

Imipenem-cilastatin:

-Rare (0.01% to 0.1%): Anaphylactic reactions

Beta-lactams:

-Frequency not reported: Hypersensitivity (anaphylactic) reactions^[Ref]

Genitourinary

Imipenem-cilastatin:

-Rare (0.01% to 0.1%): Oliguria/anuria, polyuria, urine discoloration

-Very rare (less than 0.01%): Pruritus vulvae^[Ref]

Urine discoloration was harmless (not to be confused with hematuria).^[Ref]

Respiratory

Imipenem-cilastatin:

-Very rare (less than 0.01%): Dyspnea, hyperventilation, pharyngeal pain^[Ref]

Musculoskeletal

Imipenem-cilastatin:

-Very rare (less than 0.01%): Polyarthralgia, thoracic spine pain^[Ref]