Dosing and uses of Prevpac (lansoprazole/amoxicillin/clarithromycin)
Adult dosage forms and strengths
lansoprazole/amoxicillin/clarithromycin
capsule/capsule/tablet prepack
- 30mg/500mg/500mg
- amoxicillin component consists of 2 capsules (500 mg/capsule)
Duodenal Ulcer
Eradication of H. pylori to reduce risk of duodenal ulcer recurrence
Lansoprazole 30 mg, amoxicillin 1 g, clarithromycin 500 mg administered together PO twice daily (morning and evening) for 10 or 14 days
Each dose of this combination therapy contains 4 pills: 1 capsule lansoprazole 30 mg, 2 capsules amoxicillin 500 mg, and 1 tablet clarithromycin 500 mg
Prevpac is clearly labeled for administration of 1 dose (30 mg/1 g/500 mg) PO twice daily
Renal Impairment
CrCl< 30 mL/min: Do not use
Administration
Combination therapy (lansoprazole, amoxicillin, clarithromycin) indicated for the treatment of patients with H. pylori infection and duodenal ulcer disease (active or 1-year history of a duodenal ulcer) to eradicate H. pylori
To reduce development of drug-resistant bacteria and maintain efficacy of antibacterial drugs, use only to treat or prevent infections proven or strongly suspected to be caused by susceptible bacteria
No dosage adjustment needed with hepatic impairment
Pediatric dosage forms and strengths
Safety and efficacy not established
Prevpac (lansoprazole/amoxicillin/clarithromycin) adverse (side) effects
>10%
Clarithromycin
- GI effects, general (13%)
1-10%
Clarithromycin
- Headache (6%)
- Rash (children 3%)
- Abdominal pain (adults 2%, children 3%)
- Abnormal taste (adults 3-7%)
- Diarrhea (3-6%)
- Dyspepsia (2%)
- Heartburn (adults 2%)
- GI intolerance (oral-dose related)
- Nausea (adults 3-6%)
- Vomiting (adults 1%; children 6%)
- Decreased WBC, elevated BUN (4%), elevated PT (1%)
Lansoprazole
- Fatigue (< 3%)
- Headache (2.5-4.7%)
- Abdominal pain (1.8%)
- Diarrhea (8%)
- Nausea (3.7%)
<1%
Clarithromycin
- QT prolongation
- Anxiety, dizziness, hallucinations, manic behavior, neuromuscular blockade, psychosis, seizures
- Anorexia, glossitis, pancreatitis
- AST increased, bilirubin increased, elevated LFTs, hepatic dysfunction, hepatitis, increased alkaline phosphate, jaundice
- Hypoglycemia, leukopenia, neutropenia, thrombocytopenia
- Increased serum creatinine
- Dyspnea
- Anaphylaxis, C Diff colitis, Stevens-Johnson syndrome
Frequency not defined
Amoxicillin
- Headache
- Rash
- Diarrhea, nausea, vomiting
- Anemia
- AST/ALT elevation
- Acute exanthematous pustulosis
- Exfoliative dermatitis
- Seizure
- Insomnia
- Hemorrhagic colitis
- Toxic epidermal necrolysis
- Urticaria
- Stevens-Johnson syndrome
- Anaphylaxis
- Candidiasis (mucocutaneous), pseudomembranous colitis, serum sickness
Clarithromycin
- Torsade de pointes (rare)
- Allergic reactions: urticaria & skin eruptions, leukocytoclastic vasculitis, toxic epidermal necrolysis, pruritus, rash
- Transient CNS effects: psychosis, anxiety, behavioral changes, confusional states, depersonalization, disorientation, hallucinations, insomnia, nightmares, tinnitus, tremor, and vertigo
- Hepatic failure
- Stomatitis
- Acute renal failure
- Reversible hearing loss (hypoacusis)
Warnings
Contraindications
Lansoprazole
- Hypersensitivity to lansoprazole or other proton pump inhibitors
Amoxicillin
- History of severe hypersensitivity reactions (eg, anaphylaxis or Stevens-Johnson syndrome) to amoxicillin or other beta-lactam antibiotics (eg, penicillins and cephalosporins)
- Infectious mononucleosis (relative)
Clarithromycin
- Documented hypersensitivity
- Clarithromycin/ranitidine bicitrate contraindicated in: severe renal impairment (CrCl<25 mL/min); history of acute porphyria
- QT prolongation or ventricular cardiac arrhythmia, including torsades de pointes
- Concomitant administration with HMG-CoA reductase inhibitors extensively metabolized by CYP3A4 (lovastatin or simvastatin); increases risk of myopathy, including rhabdomyolysis
Cautions
Lansoprazole
- Liver disease may require dosage reduction
- Published observational studies suggest that proton pump inhibitor (PPI) therapy may be associated with an increased risk for osteoporosis-related fractures of the hip, wrist, or spine; particularly with prolonged (>1 yr), high-dose therapy
- Hypomagnesemia may occur with prolonged use (ie, >1 year); adverse effects may result and include tetany, arrhythmias, or seizures; in 25% of cases reviewed, magnesium supplementation alone did not improve low serum magnesium levels and the PPI had to be discontinued
- PPIs possibly associated with increased incidence of Clostridium difficile-associated diarrhea (CDAD); consider diagnosis of CDAD for patients taking PPIs with diarrhea that does not improve
- Contains enteric coated granules (acid labile); do not chew or crush
- Symptomatic response to therapy with lansoprazole does not preclude the presence of gastric malignancy
- PPIs may elevate and prolong methotrexate or its metabolite serum levels, possibly leading to toxicity
Amoxicillin
- Allergy to cephalosporins, carbapenems
- Endocarditis prophylaxis: use only for high risk pts, per recent AHA Guidelines
- High doses may cause false urine glucose test by some methods
Clarithromycin
- Caution in severe renal impairment
- Do not refrigerate oral solution
- Endocarditis prophylaxis: use only for high risk patients, per recent AHA Guidelines
- Clarithromycin has been associated with prolongation of the QT interval and infrequent cases of arrhythmia
- Concomitant use of clarithromycin and oral hypoglycemic agents and/or insulin can result in significant hypoglycemia
- There is a risk of serious hemorrhage and significant elevations in INR and prothrombin time when clarithromycin is co-administered with warfarin; monitor INR and prothrombin times
Pregnancy and lactation
Pregnancy category: C ( based on the pregnancy category for clarithromycin)
No adequate and well-controlled studies in pregnant women; do not use clarithromycin in pregnant women except in circumstances in which no alternative therapy is appropriate
Lactation: Not recommended
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Prevpac (lansoprazole/amoxicillin/clarithromycin)
Mechanism of action
Lamsoprazole: Proton pump inhibitor; binds to H+/K+-exchanging ATPase (proton pump) in gastric parietal cells resulting in blocking acid secretion
Amoxicillin: Inhibits bacterial cell wall synthesis by binding to one or more penicillin binding proteins that in turn inhibit the final transpeptidation step of peptoglycan synthesis in cell wall biosynthesis
Clarithromycin: Inhibits protein synthesis by binding to 50S ribosomal subunit causing antibacterial activity
Lansoprazole
Half-Life: 0.9-1.5 hr
Bioavailability: 81-91% (empty stomach); 50-70% (30 minutes after food)
Clearance Total Body: 0.7 L/hr/kg
Onset of action: 1-3 hr (gastric acid suppression)
Renal: 517 mL/min
Metabolism: Gastric parietal cells: acidic pH converts lansoprazole to its active sulfenamide metabolites
Liver: by hepatic CYP2C19; slow metabolizers are deficient in CPY2C19 enzyme & can have plasma conc can increase 5 times or higher
Metabolites Active: cyclic sulfenamide & disulfide metaboliteInactive: 5-hydroxy-lansoprazole, sulfide metabolite, omeprazole sulfone, sulfone metabolite, hydroxysulfide metabolite, hydroxysulfone metabolite
Excretion: Feces (bile): 77%
Urine: 14-25%
Peak Plasma Time: 1.5-3 hr
Protein Bound: 97-99%
Vd: 14-18 L
Dialyzable: No
Enzymes inhibited: CYP2C19
Amoxicillin
Half-Life: 3.7 hr (neonates, full term); 1-2 hr (infants and children); 0.7-1.4 hr (adults); 7-21 hr (CrCl < 10 mL/min in adults)
Absorption: 74-92%
Distribution: most body fluids and bone, CSF<1%
Peak Plasma Time: 2hr (capsule); 3.1 hr (extended release tablet); 1 hr (suspension)
Protein Bound: 17-20%
Metabolism: Partially hepatic
Excretion: Urine
Clarithromycin
Half-Life: 3-7 hr
Peak Plasma Time: 2-3 hr (immediate release); 5-8 hr (extended release)
Absorption: Highly stable in presence of gastric acid (unlike erythromycin); food delays but does not affect extent of absorption
Distribution: Widely into most body tissues except CNs
Protein binding: 42-70%
Metabolism: partially hepatic (P450 enzyme CYP3A4); converted to 14-OH clarithromycin (active metabolite)
Renal Clearance: approximates normal GFr
Excretion: primarily urine
