What is dicloxacillin used for. Dicloxacillin: Uses, Hepatotoxicity, and Clinical Implications

15.09.202323.06.2023 by alexxlab

What is dicloxacillin used for. How does dicloxacillin work against bacterial infections. What are the potential hepatotoxic effects of dicloxacillin. How is dicloxacillin-induced liver injury managed. What precautions should be taken when prescribing dicloxacillin.

Содержание

Understanding Dicloxacillin: A Penicillinase-Resistant Antibiotic

Dicloxacillin is a second-generation penicillin antibiotic that plays a crucial role in treating bacterial infections. Its unique characteristic lies in its resistance to penicillinase, an enzyme produced by certain bacteria that can degrade many penicillin antibiotics. This resistance makes dicloxacillin particularly effective against penicillinase-producing staphylococci.

How does dicloxacillin work to combat bacterial infections? The antibiotic binds to the bacterial enzyme responsible for synthesizing peptidoglycans, which are essential components of the bacterial cell wall. By interfering with this process, dicloxacillin compromises the integrity of the bacterial cell wall, ultimately leading to the destruction of the bacteria.

Key Facts About Dicloxacillin

Approved for use in the United States in 1968
Available in 250 mg and 500 mg capsules
Also available as a suspension for pediatric use
Typical dosage: 125 to 500 mg every 6 hours

Clinical Applications of Dicloxacillin

Dicloxacillin is primarily used to treat mild-to-moderate staphylococcal infections. Its effectiveness against penicillinase-producing bacteria makes it a valuable tool in combating certain types of bacterial infections that may be resistant to other penicillins.

When should dicloxacillin be prescribed? Healthcare providers typically recommend dicloxacillin to treat or prevent infections that are proven or suspected to be caused by penicillinase-producing susceptible bacteria. This targeted approach helps reduce the development of drug-resistant bacteria, which is a growing concern in the medical community.

Common Side Effects of Dicloxacillin

While dicloxacillin is generally well-tolerated, it can cause some side effects in certain patients. These may include:

Nausea
Diarrhea
Stomatitis (inflammation of the mouth and lips)
Skin rash
Allergic reactions

Are there any severe adverse events associated with dicloxacillin use? While rare, potentially severe adverse events can occur, including anaphylaxis, Clostridium difficile diarrhea, and neutropenia. Patients should be monitored closely for these complications, especially during the initial stages of treatment.

Hepatotoxicity: A Rare but Serious Concern

One of the most significant concerns associated with dicloxacillin use is its potential for hepatotoxicity. While dicloxacillin therapy has not been associated with serum enzyme elevations during treatment, it has been linked to rare instances of clinically apparent, cholestatic hepatitis.

What are the characteristics of dicloxacillin-induced liver injury? The typical onset of liver injury occurs 1 to 6 weeks after starting treatment. The pattern of serum enzyme elevations is usually cholestatic, although cases with a mixed pattern have also been reported. Patients often present with jaundice and pruritus (itching).

Symptoms of Dicloxacillin-Induced Liver Injury

Jaundice (yellowing of the skin and eyes)
Pruritus (itching)
Occasional fever
Rare instances of rash and eosinophilia

Is dicloxacillin-induced liver injury associated with autoimmune markers? Unlike some drug-induced liver injuries, autoantibodies are rarely detected in cases of dicloxacillin-induced hepatotoxicity. This suggests that the mechanism of injury may not be primarily autoimmune-mediated.

Comparing Dicloxacillin to Similar Antibiotics

Dicloxacillin belongs to a class of antibiotics known as isoxazolyl penicillins. Other members of this class, such as flucloxacillin (also called floxacillin) and cloxacillin, have similar structures and activities. However, these antibiotics have never been approved for use or made available in the United States.

How does the hepatotoxicity of dicloxacillin compare to other isoxazolyl penicillins? Interestingly, flucloxacillin and cloxacillin have been associated with a higher frequency of cholestatic hepatitis compared to dicloxacillin. This suggests that while the potential for liver injury exists with dicloxacillin, it may be less common than with some of its structural analogues.

Other Penicillins and Cholestatic Hepatitis

It’s worth noting that cholestatic hepatitis is not unique to dicloxacillin or isoxazolyl penicillins. Similar patterns of liver injury have been observed with other penicillins, typically arising 1 to 6 weeks after starting therapy. This underscores the importance of monitoring liver function in patients receiving any penicillin antibiotic, especially during the initial weeks of treatment.

Mechanism of Dicloxacillin-Induced Liver Injury

The exact mechanism behind dicloxacillin-induced liver injury remains unclear. While allergic manifestations such as rash, fever, and eosinophilia are not common, the rapid recurrence of injury upon reexposure suggests a hypersensitivity mechanism.

What role might the beta-lactam ring play in dicloxacillin-induced liver injury? Some researchers speculate that the hypersensitivity reaction may be in response to the beta-lactam ring, a structural feature common to all penicillin antibiotics. However, more research is needed to confirm this hypothesis and elucidate the exact pathways involved in the liver injury.

Risk Factors for Dicloxacillin-Induced Liver Injury

Age: Injury appears to occur more frequently in older patients
Genetic factors: While not confirmed for dicloxacillin, similar antibiotics like flucloxacillin have shown associations with specific HLA types (e.g., HLA-B*57:01)

Are there any known genetic predispositions to dicloxacillin-induced liver injury? Currently, there are too few reported cases of dicloxacillin hepatotoxicity to draw conclusions about potential HLA associations. This is an area that warrants further investigation, especially given the known genetic links to liver injury caused by similar antibiotics.

Management and Outcomes of Dicloxacillin-Induced Liver Injury

The management of dicloxacillin-induced liver injury primarily involves discontinuation of the drug and supportive care. In the limited number of cases described, cholestasis has been prolonged, but patients typically recover clinically within 6 to 12 weeks.

Can dicloxacillin-induced liver injury lead to long-term liver damage? While most patients recover fully, some have shown evidence of residual injury. However, dicloxacillin-induced liver injury has not been linked to acute liver failure or vanishing bile duct syndrome, unlike some cases involving flucloxacillin.

Treatment Considerations

Discontinuation of dicloxacillin upon suspicion of liver injury
Supportive care and monitoring of liver function
Possible use of prednisone, although its efficacy is unclear and side effects can be serious
Avoidance of reexposure to penicillinase-resistant penicillins, including nafcillin and oxacillin

Is there a role for corticosteroids in treating dicloxacillin-induced liver injury? While prednisone has been used in some cases to treat cholestatic liver injury, its effects are not well-established. The potential benefits must be carefully weighed against the risk of serious side effects associated with corticosteroid use.

Precautions and Recommendations for Dicloxacillin Use

Given the potential for hepatotoxicity, healthcare providers should exercise caution when prescribing dicloxacillin, especially to older patients or those with pre-existing liver conditions. Regular monitoring of liver function during treatment is advisable, particularly in the first few weeks of therapy.

What steps can be taken to minimize the risk of dicloxacillin-induced liver injury? Healthcare providers should:

Carefully assess the need for dicloxacillin, considering alternative antibiotics when appropriate
Inform patients about the potential signs and symptoms of liver injury
Monitor liver function tests, especially during the initial weeks of treatment
Discontinue dicloxacillin immediately if liver injury is suspected
Advise patients to avoid future use of penicillinase-resistant penicillins if they have experienced liver injury

How should patients be counseled regarding the use of dicloxacillin? Patients should be informed about the rare but potential risk of liver injury. They should be instructed to report any symptoms such as jaundice, dark urine, light-colored stools, or persistent itching to their healthcare provider immediately.

Future Research Directions in Dicloxacillin Hepatotoxicity

While our understanding of dicloxacillin-induced liver injury has grown, many questions remain unanswered. Future research efforts could focus on several key areas to enhance our knowledge and improve patient care.

What are the priorities for future research on dicloxacillin hepatotoxicity? Some important areas of investigation include:

Elucidating the exact mechanism of liver injury
Identifying potential genetic risk factors, including HLA associations
Developing predictive models to identify patients at higher risk of liver injury
Exploring potential protective strategies or interventions to prevent or mitigate liver injury
Investigating the long-term outcomes of patients who have experienced dicloxacillin-induced liver injury

Could biomarkers play a role in early detection of dicloxacillin-induced liver injury? Research into potential biomarkers that could indicate early stages of liver injury before clinical symptoms appear could be valuable. Such markers could allow for earlier intervention and potentially better outcomes for affected patients.

Comparative Studies with Other Antibiotics

Comparative studies between dicloxacillin and other penicillinase-resistant penicillins could provide valuable insights into the relative risks and benefits of these antibiotics. Such research could help guide clinical decision-making and potentially lead to the development of safer antibiotic options.

How do the hepatotoxicity profiles of different penicillinase-resistant penicillins compare? A comprehensive comparison of the frequency, severity, and outcomes of liver injury associated with dicloxacillin, flucloxacillin, cloxacillin, and other related antibiotics could help identify any unique risk factors or protective effects associated with specific drugs in this class.

The Role of Pharmacovigilance in Monitoring Dicloxacillin Safety

Ongoing pharmacovigilance efforts play a crucial role in monitoring the safety of dicloxacillin and other antibiotics. These efforts help identify rare adverse events that may not be apparent in clinical trials and can provide valuable real-world data on drug safety.

How can healthcare providers contribute to pharmacovigilance efforts for dicloxacillin? Healthcare providers can play a vital role by:

Reporting suspected cases of dicloxacillin-induced liver injury to relevant authorities
Participating in post-marketing surveillance studies
Staying informed about the latest safety information and guidelines for dicloxacillin use
Educating patients about the importance of reporting adverse events

What role do regulatory agencies play in monitoring dicloxacillin safety? Regulatory agencies such as the FDA in the United States and the EMA in Europe continuously monitor the safety profiles of approved drugs, including dicloxacillin. They may issue safety communications, update product labeling, or take other regulatory actions based on new safety information that emerges over time.

The Importance of International Collaboration

Given the rarity of dicloxacillin-induced liver injury, international collaboration in research and pharmacovigilance efforts is crucial. Pooling data from multiple countries can provide a more comprehensive picture of the drug’s safety profile and help identify any geographical or population-specific risk factors.

How can international collaboration enhance our understanding of dicloxacillin hepatotoxicity? Collaborative efforts can facilitate:

Larger-scale epidemiological studies
Sharing of case reports and clinical experiences
Development of standardized protocols for diagnosing and managing dicloxacillin-induced liver injury
Coordination of research efforts to avoid duplication and maximize resources

Balancing the Benefits and Risks of Dicloxacillin Use

Despite the potential risk of hepatotoxicity, dicloxacillin remains an important antibiotic in the treatment of certain bacterial infections. The challenge for healthcare providers lies in balancing the clear benefits of the drug against the rare but serious risk of liver injury.

How can healthcare providers make informed decisions about dicloxacillin use? When considering prescribing dicloxacillin, providers should:

Assess the likelihood that the infection is caused by penicillinase-producing bacteria
Consider the patient’s individual risk factors for liver injury
Weigh the potential benefits of dicloxacillin against the risks of alternative antibiotics
Implement appropriate monitoring strategies during treatment
Educate patients about the signs and symptoms of liver injury to ensure early detection

What alternatives exist for patients who cannot take dicloxacillin? For patients who have experienced liver injury from dicloxacillin or are at high risk, alternative antibiotics may be considered. These could include other classes of antibiotics effective against the target bacteria, such as certain cephalosporins or vancomycin, depending on the specific infection and bacterial susceptibility.

The Importance of Antimicrobial Stewardship

The judicious use of dicloxacillin and other antibiotics is crucial not only for individual patient safety but also for broader public health concerns related to antibiotic resistance. Antimicrobial stewardship programs play a vital role in ensuring the appropriate use of antibiotics like dicloxacillin.

How can antimicrobial stewardship programs contribute to the safe use of dicloxacillin? These programs can:

Develop and implement guidelines for appropriate dicloxacillin use
Provide education to healthcare providers about the benefits and risks of dicloxacillin
Monitor prescribing patterns and provide feedback to prescribers
Implement systems to ensure appropriate dosing and duration of therapy
Promote the use of rapid diagnostic tests to guide antibiotic selection

By promoting the responsible use of dicloxacillin and other antibiotics, antimicrobial stewardship programs can help minimize the risk of adverse events while preserving the effectiveness of these important medications for future use.

Dicloxacillin – LiverTox – NCBI Bookshelf

Last Update: October 20, 2020.

OVERVIEW

Introduction

Dicloxacillin is an oral, second generation penicillin antibiotic that is used to treat bacterial infections caused by penicillinase-resistant staphylococci. Dicloxacillin has been linked to rare instances of clinically apparent, idiosyncratic liver injury.

Background

Dicloxacillin (dye klox’ a sil’ in) is a second generation penicillin that is resistant to inactivation by penicillinases and is used to treat infections caused by penicillinase-producing bacteria. Like other penicillins, dicloxacillin is a beta lactam antibiotic that is believed to act by binding to the bacterial enzyme that is responsible for synthesizing peptidoglycans which are necessary for the integrity of the bacterial cell wall. Dicloxacillin was approved for use in the United States in 1968 and is still widely used to treat mild-to-moderate staphylococcal infections. To reduce development of drug resistant bacteria, dicloxacillin is recommended to treat or prevent only those infections that are proven or suspected to be caused by penicillinase-producing susceptible bacteria. Dicloxacillin is available in multiple generic forms as 250 and 500 mg capsules and as a suspension for pediatric use. The typical dose is 125 to 500 mg every 6 hours. Common side effects of dicloxacillin include nausea, diarrhea, stomatitis, skin rash and allergic reactions. Rare but potentially severe adverse events include anaphylaxis, Clostridium difficile diarrhea and neutropenia.

Hepatotoxicity

Dicloxacillin therapy has not been associated with serum enzyme elevations during treatment, but has been linked to rare instances of clinically apparent, cholestatic hepatitis. The typical time to onset is 1 to 6 weeks and the pattern of serum enzyme elevations is usually cholestatic, although cases with a mixed pattern have also been described (Case 1). The injury usually presents with jaundice and pruritus. Fever, rash and eosinophilia can occur, but are not prominent and autoantibodies are rarely detected. A similar pattern of injury occurs more frequently with flucloxacillin (also called floxacillin) and cloxacillin, two oral isoxazolyl penicillins similar in structure and activity to dicloxacillin, but never approved for use or available in the United States. Similar cholestatic hepatitis arising 1 to 6 weeks after starting therapy occurs with other penicillins.

Likelihood score: B (highly likely but rare cause of clinically apparent liver injury).

Mechanism of Injury

The cause of the idiosyncratic, cholestatic hepatitis following dicloxacillin therapy is not known. Allergic manifestations (rash, fever and eosinophilia) are not common and the liver injury is usually not accompanied by signs or symptoms of penicillin hypersensitivity. However, the rapid recurrence of injury with reexposure suggests a hypersensitivity mechanism, perhaps in response to the beta lactam ring. Injury occurs more frequently in older patients. Too few cases of dicloxacillin hepatotoxicity have been reported to comment on possible HLA associations, such as the link to HLA-B*57:01 which has been made to flucloxacillin.

Outcome and Management

In the few cases that have been described, cholestasis has been prolonged, but all patients recovered clinically within 6 to 12 weeks, but some had evidence of residual injury. Reexposure appears to be associated with recurrence of injury, often with a shortened latency period. The idiosyncratic liver injury from dicloxacillin has not been linked to acute liver failure or the vanishing bile duct syndrome (although these have been described with similar cases due to flucloxacillin). Prednisone has been used to treat the cholestatic liver injury, but its effects are unclear while its side effects can be serious. Patients should be told to avoid reexposure to the penicillinase-resistant penicillins, including nafcillin and oxacillin.

Drug Class: Penicillin (Penicillinase-Resistant)

CASE REPORT

CHEMICAL FORMULA AND STRUCTURE

DRUG	CAS REGISTRY NO	MOLECULAR FORMULA	STRUCTURE
Dicloxacillin	Te_1_1_1_2″ rowspan=”1″ colspan=”1″>3116-76-5	C19-h27-Cl2-N3-O5-S

CITED REFERENCE

1.: Kleinman MS, Presberg JE. Cholestatic hepatitis after dicloxacillin-sodium therapy. J Clin Gastroenterol. 1986;8:77–8. [PubMed: 3701014]

ANNOTATED BIBLIOGRAPHY

References updated: 20 October 2020

Zimmerman HJ. Synthetic penicillins. In, Zimmerman HJ. Hepatotoxicity: the adverse effects of drugs and other chemicals on the liver. 2nd ed. Philadelphia: Lippincott, 1999. p. 596-8.
(Expert review of penicillins and liver injury published in 1999).
Moseley RH. Hepatotoxicity of antimicrobials and antifungal agents. In, Kaplowitz N, DeLeve LD, eds. Drug-induced liver disease. 3rd ed. Amsterdam: Elsevier, 2013, pp. 463-82.
(Review of hepatotoxicity of antibiotics mentions that liver injury from the penicillins is very rare, and is usually cholestatic for the oxypenicillins such as dicloxacillin and cloxacillin).
MacDougall C. Penicillins, cephalosporins, and other β-lactam antibiotics. In, Brunton LL, Hilal-Dandan R, Knollman BC, eds. Goodman & Gilman’s the pharmacological basis of therapeutics. 13th ed. New York: McGraw-Hill, 2018, pp. 1023-38.
(Textbook of pharmacology and therapeutics).
Kleinman MS, Presberg JE. Cholestatic hepatitis after dicloxacillin-sodium therapy. J Clin Gastroenterol. 1986;8:77–8. [PubMed: 3701014]
(56 year old man developed jaundice and pruritus 2-3 weeks after a 5 day course of dicloxacillin [bilirubin rising to 13 mg/dL, AST 225 U/L, Alk P 318 U/L], without rash, eosinophilia or fever, requiring 10 weeks to resolve).
Siegmund JB, Tarshis AM. Prolonged jaundice after dicloxacillin therapy. Am J Gastroenterol. 1993;88:1299–300. [PubMed: 8338117]
(36 year old woman developed fatigue and jaundice 3 weeks after starting dicloxacillin [bilirubin 18.2 mg/dL, ALT 100 U/L, Alk P 312 U/L], with slow recovery even with prednisone; 3 years later, enzymes were still mildly elevated [ALT 44 U/L, Alk P 188 U/L]).
Saab S, Venkataramani A, Yao F. Possible granulomatous hepatitis after dicloxacillin therapy. J Clin Gastroenterol. 1996;22:163–4. [PubMed: 8742666]
(74 year old developed rash 5 days after starting oral dicloxacillin [bilirubin 0.5 mg/dL, ALT 172 U/L, Alk P 183 U/L], biopsy showing a single granuloma and mild nonspecific changes, ultimately resolving within 4 months of stopping).
Ibáñez L, Pérez E, Vidal X, Laporte JR. Grup d’Estudi Multicènteric d’Hepatotoxicitat Aguda de Barcelona (GEMHAB). Prospective surveillance of acute serious liver disease unrelated to infectious, obstructive, or metabolic diseases: epidemiological and clinical features, and exposure to drugs. J Hepatol. 2002;37:592–600. [PubMed: 12399224]
(Survey of 107 cases of acute serious liver disease, not due to viruses, found no instances of drug induced liver injury due to penicillinase-resistant penicillins).
Björnsson E, Jerlstad P, Bergqvist A, Olsson R. Fulminant drug-induced hepatic failure leading to death or liver transplantation in Sweden. Scand J Gastroenterol. 2005;40:1095–101. [PubMed: 16165719]
(Analysis of all fatal adverse drug event reports of liver injury in Sweden between 1966 and 2002, found 103 cases; most common causes were halothane [n=16], acetaminophen [14], flucloxacillin [9], and TMP-SMZ [6]).
Hussaini SH, O’Brien CS, Despott EJ, Dalton HR. Antibiotic therapy: a major cause of drug-induced jaundice in southwest England. Eur J Gastroenterol Hepatol. 2007;19:15–20. [PubMed: 17206072]
(Review of causes of non-obstructive jaundice in 347 patients presenting between 1998 and 2004 at a single UK center, 28 were thought to be drug induced liver injury [8.1%] and antibiotics were the most common cause, 32% amoxicillin/clavulanate, 25% flucloxacillin, 18% other).
Chalasani N, Fontana RJ, Bonkovsky HL, Watkins PB, Davern T, Serrano J, Yang H, Rochon J., Drug Induced Liver Injury Network (DILIN). Causes, clinical features, and outcomes from a prospective study of drug-induced liver injury in the United States. Gastroenterology. 2008;135:1924–34. [PMC free article: PMC3654244] [PubMed: 18955056]
(Among 300 cases of drug induced liver disease in the US collected from 2004 to 2008, antimicrobials accounted for 45% of cases with 23 single agent cases due to amoxicillin/clavulanate, 13 nitrofurantoin, 10 fluoroquinolones, 9 macrolides, 9 sulfonamides, 5 cephalosporins, 3 oxacillin, 2 doxycycline, 2 amoxicillin, and one each for gentamicin, imipenem, and clindamycin, but none from dicloxacillin or nafcillin).
Devarbhavi H, Dierkhising R, Kremers WK, Sandeep MS, Karanth D, Adarsh CK. Single-center experience with drug-induced liver injury from India: causes, outcome, prognosis, and predictors of mortality. Am J Gastroenterol. 2010;105:2396–404. [PubMed: 20648003]
(313 cases of drug induced liver injury were seen over a 12 year period at a large hospital in Bangalore, India; leading causes were antituberculosis agents [58%], anticonvulsants [11%] and NSAIDs [2%]; specific antibiotic agents included sulfamethoxazole/trimethoprim [2%] and amoxicillin-clavulanate [1%]).
Ferrajolo C, Capuano A, Verhamme KMC, Schuemie M, Rossi F, Stricker BH, Sturkenboom CJM. Drug-induced hepatic injury in children: a case/non-case study of suspected adverse drug reactions in VigiBase. Br J Clin Pharmacol. 2010;70:721–8. [PMC free article: PMC2997312] [PubMed: 21039766]
(Among 624,673 adverse drug reports in children in a worldwide pharmacovigilance database, 6595 [1%] were for hepatic injury and antibacterials accounted for 11%, those with the highest adjusted odds ratios being aztreonam, erythromycin, ceftriaxone and minocycline; no mention of penicillins).
Daly AK, Donaldson PT, Bhatnagar P, Shen Y, Pe’er I, Floratos A, Daly MJ, et al. HLA-B*5701 genotype is a major determinant of drug-induced liver injury due to flucloxacillin. Nature Genetics. 2009;41:816–9. [PubMed: 19483685]
(Genome-wide association study [GWAS] in 51 cases of flucloxacillin liver injury and 285 controls found an association with a single nucleotide polymorphism linked to HLA-B*5701 [84% in cases vs 5% in controls], the same genotype associated with abacavir hypersensitivity; ~0. 2% of persons with this HLA type receiving flucloxacillin develop cholestatic hepatitis, making it likely that other genes or factors are important as well).
Reuben A, Koch DG, Lee WM., Acute Liver Failure Study Group. Drug-induced acute liver failure: results of a U.S. multicenter, prospective study. Hepatology. 2010;52:2065–76. [PMC free article: PMC3992250] [PubMed: 20949552]
(Among 1198 patients with acute liver failure enrolled in a US prospective study between 1998 and 2007, 133 were attributed to drug induced liver injury including 66 due to antimicrobial agents, but none were attributed to a penicillinase-resistant penicillin).
Daly AK. Genome-wide association studies in pharmacogenomics. Nat Rev Genet. 2010;11:241–6. [PubMed: 20300088]
(Review of recent advances in GWAS studies of pharmacokinetics and adverse drug reactions and association of flucloxacillin injury with HLA-B*5701).
Monshi MM, Faulkner L, Gibson A, Jenkins RE, Farrell J, Earnshaw CJ, Alfirevic A, et al. Human leukocyte antigen (HLA)-B*57:01-restricted activation of drug-specific T cells provides the immunological basis for flucloxacillin-induced liver injury. Hepatology. 2013;57:727–39. [PubMed: 22987284]
(T cells from persons with HLA-B*57:01 were activated when exposed to dendritic cells presenting flucloxacillin bound to albumin, and were similarly activated by oxacillin, cloxacillin and dicloxacillin).
Björnsson ES, Bergmann OM, Björnsson HK, Kvaran RB, Olafsson S. Incidence, presentation and outcomes in patients with drug-induced liver injury in the general population of Iceland. Gastroenterology. 2013;144:1419–25. [PubMed: 23419359]
(In a population based study of drug induced liver injury from Iceland, 96 cases were identified over a 2 year period, including 15 due to amoxicillin/clavulanate, 1 to dicloxacillin [2nd generation] and 1 to phenoxymethylpenicillin [1st generation], the latter two cases being anicteric).
Hernández N, Bessone F, Sánchez A, di Pace M, Brahm J, Zapata R, A, Chirino R, et al. Profile of idiosyncratic drug induced liver injury in Latin America. An analysis of published reports. Ann Hepatol. 2014;13:231–9. [PubMed: 24552865]
(Systematic review of literature of drug induced liver injury from Latin American countries published between 1996 and 2012 identified 176 cases, of which 37 [19%] were attributed to antimicrobials, but none to penicillinase resistant penicillins such as oxacillin or dicloxacillin).
Chalasani N, Bonkovsky HL, Fontana R, Lee W, Stolz A, Talwalkar J, Reddy KR, et al. United States Drug Induced Liver Injury Network. Features and outcomes of 899 patients with drug-induced liver injury: The DILIN Prospective Study. Gastroenterology. 2015;148:1340–52.e7. [PMC free article: PMC4446235] [PubMed: 25754159]
(Among 899 cases of drug induced liver injury enrolled in a US prospective study between 2004 and 2013, 323 cases [36%] were attributed to antibiotics 3 of which were due to oxacillin, all being self-limited episodes of aminotransferase elevations without jaundice; no instances of dicloxacillin or nafcillin associated liver injury).
Nicoletti P, Aithal GP, Bjornsson ES, Andrade RJ, Sawle A, Arrese M, Barnhart HX, et al. International Drug-Induced Liver Injury Consortium, Drug-Induced Liver Injury Network Investigators, and International Serious Adverse Events Consortium. Association of liver injury from specific drugs, or groups of drugs, with polymorphisms in HLA and other genes in a genome-wide association study. Gastroenterology. 2017;152:1078–89. [PMC free article: PMC5367948] [PubMed: 28043905]
(A genome-wide association study done on 862 patients with drug induced liver injury demonstrated a strong link with HLA-A*33:01 in patients with cholestatic liver injury, particularly in cases attributed to terbinafine, fenofibrate and ticlopidine).
Cirulli ET, Nicoletti P, Abramson K, Andrade RJ, Bjornsson ES, Chalasani N, Fontana RJ, et al. Drug-Induced Liver Injury Network (DILIN) investigators. International DILI consortium (iDILIC). A missense variant in PTPN22 is a risk factor for drug-induced liver injury. Gastroenterology. 2019;156:1707–1716.e2. [PMC free article: PMC6511989] [PubMed: 30664875]
(Genome-wide association studies on 2048 patients with drug-induced liver injury and 12,439 controls identified a variant in PTPN22 which was highly associated with liver injury, allele frequency being 0.12 among cases and 0.08 among controls with highest association in Northern Europeans and in cases of amoxicillin clavulanate, PTPN22 being a cellular kinase involved in modulation of immune reactions).

Dicloxacillin Oral: Uses, Side Effects, Interactions, Pictures, Warnings & Dosing

Uses

Dicloxacillin is used to treat a wide variety of bacterial infections. It is a penicillin-type antibiotic. It works by stopping the growth of bacteria.This antibiotic treats only bacterial infections. It will not work for viral infections (such as common cold, flu). Using any antibiotic when it is not needed can cause it to not work for future infections.

How to use Dicloxacillin SODIUM

Take this medication by mouth usually 4 times a day (every 6 hours), or as directed by your doctor. Take dicloxacillin on an empty stomach (1 hour before or 2 hours after a meal) with a full glass of water. Drink plenty of fluids while using this medication unless your doctor tells you otherwise.

The dosage is based on your medical condition and response to therapy.

For the best effect, take this antibiotic at evenly spaced times. To help you remember, take this medication at the same time(s) every day.

Continue to take this medication until the full-prescribed amount is finished even if symptoms disappear after a few days. Stopping the medication too early may allow bacteria to continue to grow, which may result in a relapse of the infection.

Tell your doctor if your condition lasts or gets worse.

Side Effects

Nausea, vomiting, or diarrhea may occur. If any of these effects last or get worse, tell your doctor or pharmacist promptly.

Remember that this medication has been prescribed because your doctor has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor right away if you have any serious side effects, including: nausea/vomiting that doesn’t stop, sore throat or fever that doesn’t go away, dark urine, stomach/abdominal pain, yellowing eyes/skin, easy bruising or bleeding.

This medication may rarely cause a severe intestinal condition due to a bacteria called C. difficile. This condition may occur during treatment or weeks to months after treatment has stopped. Tell your doctor right away if you develop: diarrhea that doesn’t stop, abdominal or stomach pain/cramping, blood/mucus in your stool.

If you have these symptoms, do not use anti-diarrhea or opioid products because they may make symptoms worse.

Use of this medication for prolonged or repeated periods may result in oral thrush or a new vaginal yeast infection (oral or vaginal fungal infection). Contact your doctor if you notice white patches in your mouth, a change in vaginal discharge or other new symptoms.

A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

In the US – Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch.

In Canada – Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

Precautions

Before taking dicloxacillin, tell your doctor or pharmacist if you are allergic to it; or to penicillin or cephalosporin antibiotics; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: kidney disease.

Dicloxacillin may cause live bacterial vaccines (such as typhoid vaccine) to not work well. Tell your health care professional that you are using dicloxacillin before having any immunizations/vaccinations.

During pregnancy, this medication should be used only when clearly needed. Discuss the risks and benefits with your doctor.

Dicloxacillin passes into breast milk. Consult your doctor before breast-feeding.

Interactions

Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor’s approval.

Some of the products that may interact with this drug include: mavacamten, methotrexate, tetracyclines, warfarin.

Dicloxacillin may cause false positive results with certain diabetic urine testing products (cupric sulfate-type). This drug may also affect the results of certain lab tests. Make sure laboratory personnel and your doctors know you use this drug.

Does Dicloxacillin SODIUM interact with other drugs you are taking?

Enter your medication into the WebMD interaction checker

Overdose

If someone has overdosed and has serious symptoms such as passing out or trouble breathing, call 911. Otherwise, call a poison control center right away. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center. Symptoms of overdose may include: diarrhea that doesn’t stop, severe vomiting, unusual change in the amount of urine, or seizures.

Do not share this medication with others.

This medication has been prescribed for your current condition only. Do not use it later for another infection unless your doctor tells you to.

If you are using this drug for a long time, lab and/or medical tests (such as kidney/liver function, complete blood count) should be done while you are taking this medication. Keep all medical and lab appointments. Consult your doctor for more details.

If you miss a dose, use it as soon as you remember. If it is near the time of the next dose, skip the missed dose. Use your next dose at the regular time. Do not double the dose to catch up.

Store at room temperature away from light and moisture. Do not store in the bathroom. Keep all medications away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company.