Applies to amoxicillin / clarithromycin / vonoprazan: oral capsule, oral tablet.

Serious side effects

Along with its needed effects, amoxicillin/clarithromycin/vonoprazan 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 immediately if any of the following side effects occur while taking amoxicillin / clarithromycin / vonoprazan:

Less common

• Acid or sour stomach
• anxiety
• belching
• black, tarry stools
• bladder pain
• blistering, crusting, irritation, itching, or reddening of the skin
• bloated
• bloody or cloudy urine
• blurred vision
• body aches or pain
• change in taste
• chest pain or tightness
• chills
• cold flu-like symptoms
• constipation
• cracked, dry, or scaly skin
• cough or hoarseness
• diarrhea
• difficult, burning, or painful urination
• discouragement
• dizziness
• dry mouth
• ear congestion
• excess air or gas in stomach or intestines
• eye pain
• fainting
• fast, pounding, or irregular heartbeat or pulse
• feeling sad or empty
• fever
• frequent urge to urinate
• full feeling
• general feeling of illness
• greatly decreased frequency of urination or amount of urine
• headache
• heartburn
• indigestion
• irregular heartbeat recurrent
• irritability
• itching of the vagina or genitals
• lack of appetite
• loss of interest or pleasure
• loss of taste
• loss of voice
• lower back or side pain
• nausea
• nervousness
• pain or swelling in the arms or legs without any injury
• pale skin
• passing gas
• pounding in the ears
• slow or fast heartbeat
• sneezing
• sore throat
• sores, ulcers, or white spots in the mouth or on the lips
• stomach bloating, burning, cramping, discomfort, upset, or pain
• stuffy or runny nose
• swelling around the eyes
• swelling of feet or lower legs
• swelling or inflammation of the mouth
• thick, white vaginal discharge with mild or no odor
• trouble breathing
• trouble concentrating
• trouble sleeping
• unusual bleeding or bruising
• unusual tiredness or weakness
• vomiting
• weight loss
• white or brownish vaginal discharge

Rare

• Muscle aches

Incidence not known

• Black, hairy tongue
• bleeding gums
• blistering, peeling, or loosening of the skin
• blood in the urine or stools
• cold sweats
• coma
• confusion
• confusion about identity, place, and time
• coughing up blood
• dark urine
• diarrhea, watery and severe, which may also be bloody
• difficulty swallowing
• feeling of unreality
• increased menstrual flow or vaginal bleeding
• increased thirst
• joint or muscle pain
• light-colored stools
• large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs
• muscle cramps, spasms, pains, or stiffness
• nightmares
• nosebleeds
• pains in stomach, side, or abdomen, possibly radiating to the back
• palpitations
• paralysis
• pinpoint red spots on skin
• prolonged bleeding from cuts
• puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
• red irritated eyes
• red skin lesions, often with a purple center
• seizures
• sense of detachment from self or body
• shakiness
• slurred speech
• stiff neck or back
• swollen glands
• tooth discoloration
• unpleasant breath odor
• vomiting of blood
• yellow eyes or skin

For Healthcare Professionals

Applies to amoxicillin / clarithromycin / vonoprazan: oral kit.

General

The most common adverse reactions leading to discontinuation of this product were diarrhea and hypertension.^[Ref]

Cardiovascular

Common (1% to 10%): Hypertension (includes increased blood pressure)

Frequency not reported: QT prolongation, tachycardia

Clarithromycin:

-Frequency not reported: QT interval prolongation, arrhythmia

-Postmarketing reports: Ventricular arrhythmia, torsades de pointes, hemorrhage^[Ref]

Dermatologic

Frequency not reported: Dermatitis, dry skin, rash

Amoxicillin, Clarithromycin, and Vonoprazan:

-Frequency not reported: Severe cutaneous adverse reactions (including Stevens-Johnson syndrome, toxic epidermal necrolysis)

Amoxicillin:

-Frequency not reported: Erythematous skin rash

-Postmarketing reports: Mucocutaneous candidiasis, erythematous maculopapular rashes, erythema multiforme, exfoliative dermatitis, urticaria, toxic epidermal necrolysis, Stevens-Johnson syndrome, drug reaction with eosinophilia and systemic symptoms (DRESS), acute generalized exanthematous pustulosis (AGEP)

Clarithromycin:

-Postmarketing reports: Angioedema, toxic epidermal necrolysis, Stevens-Johnson syndrome, DRESS, AGEP, Henoch-Schonlein purpura, acne

Vonoprazan:

-Postmarketing reports: Urticaria, drug eruption, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis^[Ref]

Gastrointestinal

Common (1% to 10%): Diarrhea, abdominal pain (includes abdominal discomfort, abdominal pain, lower abdominal pain, upper abdominal pain)

Frequency not reported: Abdominal distension, constipation, dry mouth, duodenal polyp, duodenal ulcer, dyspepsia, flatulence, gastric ulcer, gastroesophageal reflux disease, hematochezia, large intestine polyp, nausea, rectal polyp, stomatitis, tongue discomfort, vomiting, anal fungal infection, gastrointestinal viral infection, oral fungal infection, tongue fungal infection

Amoxicillin:

-Frequency not reported: Clostridioides difficile-associated diarrhea

-Postmarketing reports: Black hairy tongue, hemorrhagic/pseudomembranous colitis, tooth discoloration (brown, yellow, or gray staining)

Clarithromycin:

-Frequency not reported: C difficile-associated diarrhea

-Postmarketing reports: Acute pancreatitis, tongue discoloration, tooth discoloration, pseudomembranous colitis

Acid-Suppressing Therapies:

-Frequency not reported: C difficile-associated diarrhea^[Ref]

Onset of pseudomembranous colitis symptoms has been reported during or after antibacterial treatment.

Most reports of tooth discoloration with amoxicillin occurred in pediatric patients; discoloration was reduced/eliminated with brushing or dental cleaning in most cases.

Tooth discoloration with clarithromycin was usually reversible with professional cleaning after the drug was discontinued.^[Ref]

Genitourinary

Common (1% to 10%): Vulvovaginal candidiasis (includes urogenital fungal infection, vulvovaginal candidiasis, vulvovaginal mycotic infection, vulvovaginal pruritus, genital pruritus, genital fungal infection)

Frequency not reported: Urinary tract infection, vaginal discharge

Amoxicillin:

-Postmarketing reports: Crystalluria

Clarithromycin:

-Postmarketing reports: Abnormal urine color (associated with hepatic failure)^[Ref]

Hematologic

Hemolytic anemia, thrombocytopenia, thrombocytopenic purpura, eosinophilia, and agranulocytosis have been reported during therapy with penicillins; these reactions were usually reversible when therapy was stopped and were believed to be hypersensitivity phenomena.^[Ref]

Frequency not reported: Anemia, leukocytosis, leukopenia, neutropenia

Clarithromycin:

-Postmarketing reports: Thrombocytopenia, agranulocytosis, prolonged prothrombin time, decreased WBC count, increased INR

Penicillins:

-Postmarketing reports: Hemolytic anemia, thrombocytopenia, thrombocytopenic purpura, eosinophilia, agranulocytosis^[Ref]

Hepatic

Adverse reactions related to hepatic dysfunction have been reported with clarithromycin.^[Ref]

Frequency not reported: Abnormal liver function test

Clarithromycin:

-Frequency not reported: Cholestatic hepatitis, jaundice

-Postmarketing reports: Hepatic failure, hepatocellular jaundice, hepatic dysfunction (including increased liver enzymes)

Vonoprazan:

-Postmarketing reports: Hepatic injury, hepatic failure, jaundice^[Ref]

Hypersensitivity

Frequency not reported: Drug hypersensitivity

Amoxicillin, Clarithromycin, and Vonoprazan:

-Frequency not reported: Hypersensitivity reactions (e.g., anaphylaxis, anaphylactic shock, rash, erythema multiforme, Henoch-Schonlein purpura)

Amoxicillin:

-Postmarketing reports: Anaphylaxis, serum sickness-like reactions, hypersensitivity vasculitis

Clarithromycin:

-Postmarketing reports: Anaphylactic reactions

Vonoprazan:

-Postmarketing reports: Anaphylactic shock^[Ref]

Metabolic

Hypoglycemia has been reported in patients taking clarithromycin with oral hypoglycemic agents or insulin.^[Ref]

Frequency not reported: Decreased appetite

Clarithromycin:

-Postmarketing reports: Hypoglycemia^[Ref]

Musculoskeletal

Frequency not reported: Bone fracture

Clarithromycin:

-Postmarketing reports: Myopathy, rhabdomyolysis^[Ref]

Rhabdomyolysis was reported and in some of the reports, clarithromycin was coadministered with statins, fibrates, colchicine, or allopurinol.^[Ref]

Nervous system

Common (1% to 10%): Dysgeusia (includes taste disorder), headache

Frequency not reported: Ageusia, dizziness, tension headache

Amoxicillin:

-Postmarketing reports: Reversible hyperactivity, convulsions, aseptic meningitis

Clarithromycin:

-Frequency not reported: New onset of symptoms of myasthenic syndrome, exacerbation of symptoms of myasthenia gravis

-Postmarketing reports: Parosmia, anosmia, paresthesia, convulsions^[Ref]

Ocular

Frequency not reported: Orbital edema^[Ref]

Other

Deafness was reported primarily in elderly women and was usually reversible.^[Ref]

Frequency not reported: Fatigue, pyrexia, viral infection

Clarithromycin:

-Postmarketing reports: Deafness^[Ref]

Psychiatric

Abnormal behavior, confusional state, depersonalization, disorientation, hallucination, manic behavior, abnormal dream, and psychotic disorder usually resolved when clarithromycin was discontinued.^[Ref]

Frequency not reported: Anxiety, depression, insomnia

Amoxicillin:

-Postmarketing reports: Agitation, confusion, behavioral changes

Clarithromycin:

-Postmarketing reports: Abnormal behavior, confusional state, depersonalization, disorientation, hallucination, manic behavior, abnormal dream, psychotic disorder^[Ref]

Renal

Frequency not reported: Renal hypertrophy, tubulointerstitial nephritis

Clarithromycin:

-Postmarketing reports: Renal failure^[Ref]

Respiratory

Uncommon (0.1% to 1%): Nasopharyngitis

Frequency not reported: Pneumonia, upper respiratory tract infection, cough, nasal polyps, oropharyngeal pain^[Ref]