Source: FDA, National Drug Code (US) Revision Year: 2023
In adults, symptomatic response to therapy with VOQUEZNA does not preclude the presence of gastric malignancy. Consider additional follow-up and diagnostic testing in patients who have a suboptimal response or an early symptomatic relapse after completing treatment with VOQUEZNA. In older patients, also consider endoscopy.
Acute tubulointerstitial nephritis (TIN) has been reported with VOQUEZNA [see Adverse Reactions (6.1)]. If suspected, discontinue VOQUEZNA and evaluate patients with suspected acute TIN.
Published observational studies suggest that proton pump inhibitors (PPIs) may be associated with an increased risk of Clostridioides difficile-associated diarrhea (CDAD), especially in hospitalized patients. VOQUEZNA, another drug that blocks the proton pump to inhibit gastric acid production, may also increase the risk of CDAD. Consider CDAD in patients with diarrhea that does not improve [see Adverse Reactions (6.2)]. Use the shortest duration of VOQUEZNA appropriate to the condition being treated.
CDAD has been reported with use of nearly all antibacterial agents. For more information specific to antibacterial agents (clarithromycin and amoxicillin) indicated for use in combination with VOQUEZNA, refer to Warnings and Precautions section of the corresponding prescribing information.
Several published observational studies suggest that PPI therapy may be associated with an increased risk for osteoporosis-related fractures of the hip, wrist or spine. The risk of fracture was increased in patients who received high-dose, defined as multiple daily doses, and long-term therapy (a year or longer). Bone fracture, including osteoporosis-related fracture, has also been reported with vonoprazan. Use the shortest duration of VOQUEZNA appropriate to the condition being treated [see Dosage and Administration (2.1)]. Patients at risk for osteoporosis-related fractures should be managed according to the established treatment guidelines.
Severe cutaneous adverse reactions, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported with VOQUEZNA [see Adverse Reactions (6.2)].
Discontinue VOQUEZNA at the first signs or symptoms of severe cutaneous adverse reactions or other signs of hypersensitivity and consider further evaluation.
Long-term use of acid-suppressing drugs can lead to malabsorption of Vitamin B12 caused by hypo- or achlorhydria. Vitamin B12 deficiency has been reported postmarketing with vonoprazan [see Adverse Reactions (6.2)]. If clinical symptoms consistent with Vitamin B12 deficiency are observed in patients treated with VOQUEZNA consider further workup.
Hypomagnesemia has been reported postmarketing with vonoprazan [see Adverse Reactions (6.2)]. Hypomagnesemia may lead to hypocalcemia and/or hypokalemia and may exacerbate underlying hypocalcemia in at-risk patients.
Consider monitoring magnesium levels prior to initiation of VOQUEZNA and periodically in patients expected to be on prolonged treatment, in patients taking drugs that may have increased toxicity in the presence of hypomagnesemia (e.g., digoxin), or drugs that may cause hypomagnesemia (e.g., diuretics). Treatment of hypomagnesemia may require magnesium replacement and discontinuation of VOQUEZNA.
Consider monitoring magnesium and calcium levels prior to initiation of VOQUEZNA and periodically while on treatment in patients with a preexisting risk of hypocalcemia (e.g., hypoparathyroidism). Supplement with magnesium and/or calcium, as necessary. If hypocalcemia is refractory to treatment, consider discontinuing VOQUEZNA.
Serum chromogranin A (CgA) levels increase secondary to drug-induced decreases in gastric acidity. The increased CgA level may cause false positive results in diagnostic investigations for neuroendocrine tumors. Temporarily discontinue VOQUEZNA treatment at least 14 days before assessing CgA levels and consider repeating the test if initial CgA levels are high. If serial tests are performed (e.g., for monitoring), the same commercial laboratory should be used for testing, as reference ranges between tests may vary [see Drug Interactions (7) and Clinical Pharmacology (12.2)].
Use of VOQUEZNA is associated with a risk of fundic gland polyps that increases with long-term use, especially beyond one year. Fundic gland polyps have been reported with vonoprazan in clinical trials and postmarketing use with PPIs. Most patients who developed fundic gland polyps were asymptomatic and fundic gland polyps were identified incidentally on endoscopy. Use the shortest duration of VOQUEZNA appropriate to the condition being treated [see Dosage and Administration (2.1)].
The following serious adverse reactions are described elsewhere in labeling:
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.
The safety of VOQUEZNA was evaluated in a randomized, active-controlled, double-blind two phase trial for the healing of erosive esophagitis (2 to 8 weeks) and maintenance of healed erosive esophagitis (through 24 weeks) conducted in the United States and Europe [see Clinical Studies (14.1), (14.2)].
Adverse reactions reported in at least 2% of patients in the VOQUEZNA arm in the healing phase are presented in Table 5.
Table 5. Adverse Reactions* in a Clinical Trial of Adult Patients with All Grades of Erosive Esophagitis† (2 to 8 Week Healing Phase):
| Adverse Reactions | VOQUEZNA 20 mg Once Daily N=514 % | Lansoprazole 30 mg Once Daily N=510 % |
|---|---|---|
| Gastritis‡ | 3 | 2 |
| Diarrhea‡ | 2 | 3 |
| Abdominal distension | 2 | 1 |
| Abdominal pain‡ | 2 | 1 |
| Nausea | 2 | 1 |
* Reported in at least 2% of patients in the VOQUEZNA arm.
† The trial was not designed to support comparative claims for VOQUEZNA for the adverse reactions reported in this table.
‡ Represents a grouped term and includes related terms.
Adverse reactions reported in at least 3% of patients in the VOQUEZNA arm of the maintenance phase are shown in Table 6.
Table 6. Adverse Reactions* in a Clinical Trial of Adult Patients with All Grades of Erosive Esophagitis† (24 Week Maintenance Phase):
| Adverse Reactions | VOQUEZNA 10 mg Once Daily N=296 % | Lansoprazole 15 mg Once Daily N=297 % |
|---|---|---|
| Gastritis‡ | 6 | 3 |
| Abdominal pain‡ | 4 | 2 |
| Dyspepsia | 4 | 3 |
| Hypertension‡ | 3 | 2 |
| Urinary tract infection | 3 | 2 |
* Reported in at least 3% of patients in the VOQUEZNA arm.
† The trial was not designed to support comparative claims for VOQUEZNA for the adverse reactions reported in this table.
‡ Represents grouped term and includes related terms.
COVID-19 was reported in the healing phase in 11 (2%) VOQUEZNA-treated subjects and 9 (2%) lansoprazole-treated subjects; and in the maintenance phase in 18 (6%) VOQUEZNA-treated subjects and 20 (7%) lansoprazole-treated subjects.
Adverse reactions reported in the United States trial were similar to those reported in 4 additional randomized, active-controlled, double-blind studies of vonoprazan compared to lansoprazole conducted outside of the United States (two eight-week trials of healing of erosive esophagitis and two 24-week maintenance of healed erosive esophagitis trials).
Adverse reactions reported in 1% or less of VOQUEZNA-treated patients in the healing or maintenance phase of the United States trial are:
Blood and lymphatic system disorders: anemia, lymphocytosis
Cardiac disorders: tachycardia
Ear and labyrinth disorders: vertigo
Gastrointestinal disorders: duodenal polyp, dry mouth, dysphagia, eructation, flatulence, gastric polyps, vomiting
General disorders and administrative site conditions: asthenia, peripheral edema
Infections and infestations: upper respiratory infection
Investigations: increased liver function test
Metabolism and nutritional disorders: diabetes mellitus
Musculoskeletal system: bone fracture
Nervous system disorders: dizziness, headache, syncope
Psychiatric disorders: depression, insomnia
Renal and urinary disorders: tubulointerstitial nephritis
Skin and subcutaneous tissue disorders: eczema, rash, urticaria
The safety of VOQUEZNA, amoxicillin and clarithromycin was evaluated in 675 adult patients (aged 20 to 82 years) in clinical trials in the United States, Europe and Japan and VOQUEZNA and amoxicillin was evaluated in 348 adult patients (aged 20 to 80 years) in a clinical trial in the United States and Europe. All of the patients were screened and found to be positive for H. pylori infection.
The safety of VOQUEZNA, amoxicillin and clarithromycin (triple therapy) and VOQUEZNA and amoxicillin (dual therapy) was evaluated in a randomized, controlled, double-blind (triple therapy)/open-label (dual therapy) study conducted in the United States and Europe in treatment-naïve H. pylori-positive adult patients [see Clinical Studies (14.3)].
Treatment discontinuation due to an adverse reaction occurred in 2.3% (8/346) of the patients treated with VOQUEZNA, amoxicillin and clarithromycin, 0.9% (3/348) of the patients treated with VOQUEZNA and amoxicillin, and 1.2% (4/345) of the patients treated with lansoprazole, amoxicillin and clarithromycin. The most common adverse reactions leading to discontinuation of VOQUEZNA, amoxicillin and clarithromycin were diarrhea (0.6%) and hypertension (0.6%) and the most common adverse reaction leading to discontinuation of VOQUEZNA and amoxicillin was rash (0.6%).
Adverse reactions reported in at least 2% of patients in any treatment arm are described in Table 7.
Table 7. Adverse Reactions* in Adult Patients with H. pylori Infection†:
| Adverse Reactions | VOQUEZNA and Amoxicillin | VOQUEZNA, Amoxicillin, and Clarithromycin | Lansoprazole, Amoxicillin, and Clarithromycin |
|---|---|---|---|
| N=348 % | N=346 % | N=345 % | |
| Diarrhea | 5 | 4 | 10 |
| Dysgeusia‡ | 1 | 5 | 6 |
| Vulvovaginal candidiasis‡ | 2 | 3 | 1 |
| Abdominal pain‡ | 3 | 2 | 3 |
| Headache | 1 | 3 | 1 |
| Hypertension‡ | 1 | 2 | 1 |
| Nasopharyngitis | 2 | <1 | 1 |
* Reported in at least 2% of patients in any treatment arm.
† These trials were not designed to support comparative claims for VOQUEZNA-containing treatment arms for the adverse reactions reported in this table.
‡ Represents grouped term and includes related terms.
Other adverse reactions reported in less than 2% of patients treated with VOQUEZNA, amoxicillin, and clarithromycin or VOQUEZNA and amoxicillin are listed below by body system:
Blood and lymphatic system disorders: anemia, leukocytosis, leukopenia, neutropenia
Cardiac disorders: QT prolongation, tachycardia
Eye disorders: orbital edema
Gastrointestinal disorders: abdominal distension, constipation, dry mouth, duodenal polyp, duodenal ulcer, dyspepsia, flatulence, gastric ulcer, gastroesophageal reflux disease, hematochezia, large intestine polyp, rectal polyp, nausea, stomatitis, tongue discomfort, vomiting
General disorders and administration site conditions: fatigue, pyrexia
Immune system disorders: drug hypersensitivity
Infections and infestations: anal fungal infection, gastrointestinal viral infection, oral fungal infection, pneumonia, tongue fungal infection, upper respiratory tract infection, urinary tract infection, viral infection
Investigations: increased liver function test
Metabolism and nutrition disorders: decreased appetite
Musculoskeletal system: bone fracture
Nervous system disorders: ageusia, dizziness, tension headache
Psychiatric disorders: anxiety, depression, insomnia
Renal and urinary disorders: renal hypertrophy, tubulointerstitial nephritis
Reproductive system and breast disorders: vaginal discharge
Respiratory, thoracic and mediastinal disorders: cough, nasal polyps, oropharyngeal pain
Skin and subcutaneous tissue disorders: dermatitis, dry skin, rash
For more information on adverse reactions and laboratory changes with amoxicillin or clarithromycin, refer to Adverse Reactions section of the corresponding prescribing information.
The following additional adverse reactions have been identified during post-approval use of vonoprazan outside of the United States. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Blood and lymphatic system disorders: thrombocytopenia
Immune system disorders: anaphylactic shock [see Contraindications (4)]
Infections and infestations: C. difficile (with concomitant antibacterials) [see Warnings and Precautions (5.3)]
Investigation: hypomagnesemia, hypokalemia, hypocalcemia, vitamin B12 deficiency [see Warnings and Precautions (5.6), (5.7)]
Hepatobiliary disorders: hepatic injury, hepatic failure, jaundice
Skin and subcutaneous tissue disorders: drug eruption, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis [see Warnings and Precautions (5.5)]
Table 8 and Table 9 include drugs with clinically important drug interactions and interaction with diagnostics when administered concomitantly with VOQUEZNA and instructions for preventing or managing them.
These recommendations are based on either drug interaction trials or predicted interactions due to the expected magnitude of interaction and potential for serious adverse reactions or loss of efficacy [see Clinical Pharmacology (12.3)].
Consult the labeling of concomitantly used drugs to obtain further information about interactions with vonoprazan.
Table 8. Drug Interactions Affecting Drugs Co-Administered with VOQUEZNA and Interactions with Diagnostics:
| Drugs Dependent on Gastric pH for Absorption | ||
| Antiretrovirals | ||
| Clinical Effect | Vonoprazan reduces intragastric acidity [see Clinical Pharmacology (12.2)] which may alter the absorption of antiretroviral drugs leading to changes in the safety and/or effectiveness. | |
| Prevention or Management | Rilpivirine-containing products | Concomitant use with VOQUEZNA is contraindicated. |
| Atazanavir | Avoid concomitant use with VOQUEZNA. | |
| Nelfinavir | ||
| Other antiretrovirals | See the prescribing information of other antiretroviral drugs dependent on gastric pH for absorption prior to concomitant use with VOQUEZNA. | |
| Other Drugs (e.g., iron salts, erlotinib, dasatinib, nilotinib, mycophenolate mofetil, ketoconazole/itraconazole) | ||
| Clinical Effect | Vonoprazan reduces intragastric acidity [see Clinical Pharmacology (12.2)], which may decrease the absorption of drugs reducing their effectiveness. | |
| Prevention or Management | See the prescribing information for other drugs dependent on gastric pH for absorption. | |
| Combination Therapy with Clarithromycin and/or Amoxicillin | ||
| Clinical Effect | Concomitant administration of clarithromycin with other drugs can lead to serious adverse reactions, including potentially fatal arrhythmias, and are contraindicated. Amoxicillin also has drug interactions. | |
| Prevention or Management | See Contraindications and Warnings and Precautions in the prescribing information for clarithromycin. See Drug Interactions in the prescribing information for amoxicillin. | |
| Certain CYP3A Substrates where minimal concentration changes may lead to serious toxicities | ||
| Clinical Effect | Vonoprazan is a weak CYP3A inhibitor [see Clinical Pharmacology (12.3)]. Vonoprazan may increase exposure of CYP3A4 substrates, which may increase the risk of adverse reactions related to these substrates. | |
| Prevention or Management | Frequent monitoring for concentrations and/or adverse reactions related to the substrate drugs when used with VOQUEZNA. Dosage reduction of substrate drugs may be needed. See prescribing information for the relevant substrate drugs. | |
| CYP2C19 Substrates (e.g., clopidogrel, citalopram, cilostazol) | ||
| Clinical Effect | Vonoprazan is a CYP2C19 inhibitor [see Clinical Pharmacology (12.3)]. Vonoprazan may reduce plasma concentrations of the active metabolite of clopidogrel and may cause reduction in platelet inhibition. Vonoprazan may increase exposure of CYP2C19 substrate drugs (e.g., citalopram, cilostazol). | |
| Prevention or Management | Clopidogrel | Carefully monitor the efficacy of clopidogrel and consider alternative anti-platelet therapy. |
| Citalopram and Cilostazol | Carefully monitor patients for adverse reactions associated with citalopram and cilostazol. See the prescribing information for dosage adjustments. | |
| Chromogranin (CgA) Test for Neuroendocrine Tumors | ||
| Clinical Effect | Vonoprazan reduces intragastric acidity [see Clinical Pharmacology (12.2)], which increases CgA levels and may cause false positive results in diagnostic investigations for neuroendocrine tumors. | |
| Prevention or Management | Assess CgA levels at least 14 days after stopping VOQUEZNA treatment and repeat the test if initial CgA levels are high. If serial tests are performed (e.g., for monitoring), use the same commercial laboratory for testing, as reference ranges between tests may vary. | |
| Interaction with Secretin Stimulation Test | ||
| Clinical Effect | Hyper-response in gastrin secretion in response to secretin stimulation test, falsely suggesting gastrinoma. | |
| Prevention or Management | Temporarily stop VOQUEZNA at least 14 days before assessing to allow gastrin levels to return to baseline [see Clinical Pharmacology (12.2)]. | |
Table 9. Drug Interactions Affecting VOQUEZNA When Co-Administered with Other Drugs:
| Strong or Moderate CYP3A4 Inducers | |
| Clinical Effect | Vonoprazan is a CYP3A substrate. Strong or moderate CYP3A inducers decrease vonoprazan exposure [see Clinical Pharmacology (12.3)], which may reduce the effectiveness of VOQUEZNA. |
| Prevention or Management | Avoid concomitant use with VOQUEZNA. |
There are no adequate and well-controlled studies of vonoprazan in pregnant women. Available data from pharmacovigilance reports with vonoprazan-containing products use in pregnant women are not sufficient to evaluate for a drug-associated risk for major birth defects, miscarriage, or other adverse maternal or fetal outcomes.
In pregnant rats, no adverse effects were noted after oral administration of vonoprazan during organogenesis at approximately 27-times the maximum recommended human dose (MRHD) based on AUC exposure comparisons.
In a pre- and postnatal development (PPND) study, pups from dams orally administered vonoprazan during organogenesis and through lactation, exhibited liver discoloration, which in follow-up mechanistic animal studies was associated with necrosis, fibrosis, and hemorrhage at a dose approximately 22-times the MRHD based on AUC comparisons which were likely attributable to exposure during lactation [see Use in Specific Populations (8.2)]. These effects were not observed at the next lower dose in this study, which was approximately equal to the MRHD based on AUC comparison, however they were seen at clinically relevant exposures in dose range finding studies in rats (see Data).
The estimated background risks of major birth defects and miscarriage for the indicated population are unknown. All pregnancies have a background risk of birth defects, loss, or other adverse outcomes. In the United States general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Report pregnancies to the Phathom Pharmaceuticals, Inc. Adverse Event reporting line at 1-888-775-7428.
Pregnant rats were orally administered vonoprazan at doses of 30, 100, or 300 mg/kg/day (7-, 27-, 130-times the MRHD based on AUC comparison at the same doses from unmated female rats from separate studies) during the period of organogenesis from gestation day (GD) 6 to 17. During maternal dosing, one high-dose female died and decreased body weight and food consumption occurred at the middle and highest doses. No embryo-fetal lethality was observed but decreased fetal body weight was observed in the highest dose group. Fetal abnormalities were limited to the 300 mg/kg/day and included ventricular septal defect and mal-positioned subclavian artery in fetuses in a majority (15/19) of litters, as well as tail abnormalities and small anal opening. No adverse embryo-fetal effects were observed at the 100 mg/kg/day.
Pregnant rabbits were orally administered vonoprazan at doses of 3, 10, or 30 mg/kg/day (0.04-, 1.5-, 10-times the MRHD based on AUC comparison) during the period of organogenesis from GD 6 to 18. Two animals aborted at the highest dose and decreased body weight and food consumption occurred at the mid and high doses. No embryo-fetal mortality or toxicity occurred. There were no external, visceral or skeletal abnormalities.
In a PPND study, pregnant female rats were orally administered vonoprazan at doses of 1, 3, 10, or 100 mg/kg/day (0.01-, 0.18-, 1.1-, 22-times the MRHD based on AUC comparison) from GD 6 to lactation day (LD) 21. Decreased body weight gain and food consumption were present in dams at the highest dose during lactation. Decreased body weight gain compared to controls was observed in the offspring from dams in the high dose group. Liver discoloration occurred in offspring from the high dose group at LD 4 but was not present in animals examined after weaning. Similarly, in dose range finding studies in rats and follow-up mechanistic animal studies, the liver discoloration was observed and characterized as necrosis, fibrosis, and hemorrhage at equal to or greater than clinically relevant exposures based on AUC comparisons. The mechanistic studies further demonstrated the effect was likely attributable to vonoprazan exposure during lactation [see Use in Specific Populations (8.2)]. The clinical relevance of the liver findings is uncertain.
Exposure margins from vonoprazan between the animal and clinical studies for vonoprazan, amoxicillin and clarithromycin used in combination may be lower due to increased vonoprazan exposure from concomitant use with clarithromycin in patients [see Clinical Pharmacology (12.3)].
There are no data regarding the presence of vonoprazan in human milk, the effects on the breastfed infant, or the effects on milk production. Vonoprazan and its metabolites are present in rat milk. Liver injury occurred in offspring from pregnant and lactating rats administered oral vonoprazan at AUC exposures approximately equal to and greater than the MRHD (see Data). When a drug is present in animal milk, it is likely that the drug will be present in human milk. Because of the potential risk of adverse liver effects shown in animal studies with vonoprazan, advise patients not to breastfeed during treatment with VOQUEZNA.
In a PPND study in rats, in which the dams were administered oral vonoprazan during gestation and through lactation at up to 22-times the MRHD (based on AUC comparison), liver discoloration occurred in offspring from the high dose group [see Use in Specific Populations (8.1)].
Liver discoloration associated with necrosis, fibrosis, and hemorrhage in the offspring of dosed rats was also seen in dose-range finding studies and follow-up, mechanistic studies, including offspring in lactation only studies. These effects were reported in pups on LD 4 at doses from 3 to 100 mg/kg/day (approximately 0.2- to 22-fold the MRHD based on AUC values extrapolated from the PPND study) and on LD 14 at doses from 10 to 100 mg/kg/day dose groups (approximately 1- to 22-fold the MRHD based on an extrapolated AUC comparisons). In mechanistic studies, liver effects were observed in offspring treated only during lactation but not in offspring from animals only treated during gestation. In some of these studies, this finding was associated with increased offspring stomach weights that was reversed along with liver discoloration by concomitant treatment with a gastrointestinal prokinetic agent.
The safety and effectiveness of VOQUEZNA have not been established in pediatric patients.
There were 200 patients aged 65 years and older in the clinical trial for erosive esophagitis and relief of heartburn [see Clinical Studies (14.1)]. Of the total number of vonoprazan-treated patients there were 93 (18%) patients aged 65 years of age and older and 10 (2%) patients aged 75 years of age and older.
There were 218 patients aged 65 years and older in the clinical trial for the treatment of H. pylori infection [see Clinical Studies (14.3)]. Of the total number of vonoprazan-treated patients, there were 153 (22%) patients aged 65 years of age and older and 18 (3%) patients aged 75 years of age and older.
No overall differences in safety or effectiveness were observed between these patients and younger adult patients, and other reported clinical experience has not identified differences in responses between the geriatric and younger adult patients, but greater sensitivity of some older individuals cannot be ruled out.
No clinically meaningful differences in the pharmacokinetics of vonoprazan are predicted in patients 65 years of age and older compared to younger adult patients [see Clinical Pharmacology (12.3)].
No dosage adjustment of VOQUEZNA for the healing of erosive esophagitis is recommended in patients with mild to moderate renal impairment (eGFR 30 to 89 mL/min). Dosage reduction is recommended in patients with severe renal impairment (eGFR <30 mL/min) [see Dosage and Administration (2.2) and Clinical Pharmacology (12.3)].
No dosage adjustment of VOQUEZNA for the maintenance of healed erosive esophagitis is recommended in patients with any degree of renal impairment.
Use of VOQUEZNA is not recommended for the treatment of H. pylori infection in patients with severe renal impairment (eGFR <30 mL/min) [see Dosage and Administration (2.2) and Clinical Pharmacology (12.3)].
No dosage adjustment of VOQUEZNA for the healing of erosive esophagitis is recommended in patients with mild hepatic impairment (Child-Pugh A). Dosage reduction is recommended in patients with moderate to severe hepatic impairment (Child-Pugh Class B and C) [see Dosage and Administration (2.3) and Clinical Pharmacology (12.3)].
No dosage adjustment of VOQUEZNA for the maintenance of healed erosive esophagitis is recommended in patients with any degree of hepatic impairment.
Use of VOQUEZNA is not recommended for the treatment of H. pylori infection in patients with moderate to severe hepatic impairment (Child-Pugh Class B and C) [see Dosage and Administration (2.3) and Clinical Pharmacology (12.3)].
© All content on this website, including data entry, data processing, decision support tools, "RxReasoner" logo and graphics, is the intellectual property of RxReasoner and is protected by copyright laws. Unauthorized reproduction or distribution of any part of this content without explicit written permission from RxReasoner is strictly prohibited. Any third-party content used on this site is acknowledged and utilized under fair use principles.
