PENICILLIN

Classification | Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

Specific Substances

1) AMINOPENICILLINS

a) Amoxicillin (synonym)
b) Amoxicillin/potassium clavulanate (synonym)
c) Ampicillin (synonym)
d) Ampicillin/sulbactam (synonym)
e) Bacampicillin (synonym)

2) EXTENDED SPECTRUM

a) Carbenicillin (synonym)
b) Mezlocillin (synonym)
c) Piperacillin (synonym)
d) Piperacillin/tazobactam sodium (synonym)
e) Ticarcillin (synonym)
f) Ticarcillin/potassium clavulanate (synonym)

3) NATURAL PENICILLINS

a) PCN
b) Penicillin G (synonym)
c) Penicillin V (synonym)

4) PENICILLINASE-RESISTANT

a) Cloxacillin (synonym)
b) Dicloxacillin (synonym)
c) Methicillin (synonym)
d) Nafcillin (synonym)
e) Oxacillin (synonym)

Available Forms Sources

1) Amoxicillin: 125 mg and 250 mg chewable tablets; 250 mg and 500 mg capsules; 50 mg/mL, 125 mg/5 mL, and 250 mg/5 mL powder for oral suspension
2) Ampicillin: 250 mg and 500 mg tablets; 100 mg/5 mL, 125 mg/5 mL, 250 mg/5 mL, and 500 mg/5 mL powder for oral solution; 125 mg, 250 mg, 500 mg, 1 g, 2 g, and 10 g powder for injection
3) Bacampicillin: 400 mg tablets; 125 mg/5 mL powder for oral suspension
4) Cloxacillin: 250 mg and 500 mg capsules; 125 mg/5 mL powder for oral suspension
5) Dicloxacillin: 125 mg, 250 mg, and 500 mg capsules; 62.5 mg/5 mL powder for oral suspension
6) Methicillin: 1 g, 4 g, 6 g, and 10 g powder for injection
7) Mezlocillin: 1 g, 2 g, 3 g, 4 g, and 20 g powder for injection
8) Nafcillin: 500 mg tablets; 250 mg capsules; 500 mg, 1 g, 2 g, and 10 g powder for injection
9) Oxacillin: 250 mg and 500 mg capsules; 250 mg/5 mL powder for oral solution; 250 mg, 500 mg, 1 g, 2 g, 4 g, and 10 g powder for injection
10) Penicillin G Benzathine: 300,000 units/mL, 600,000 units/unit dose, 1,200,000 units/dose, and 2,400,000 units/dose injections
11) Penicillin G Potassium: 200,000 units, 250,000 units, 400,000 units, 500,000 units, and 800,000 units tablets; 400,000 units/5 mL powder for oral solution; 1 mu, 2 mu, and 3 mu premixed injection; 1 mu, 5 mu, 10 mu, and 20 mu powder for injection
12) Penicillin G Sodium: 5,000,000 units/vial powder for injection
13) Penicillin V: 125 mg, 250 mg, and 500 mg tablets; 125 mg/5 mL and 250 mg/5 mL powder for injection
14) Piperacillin: 2 g, 3 g, 4 g, and 40 g powder for injection
15) Ticarcillin: 1 g, 3 g, 6 g, 20 g, and 30 g powder for injection

1) Penicillins are indicated in the treatment of mildly to moderately severe infections caused by a variety of gram-positive, gram-negative, and anaerobic microorganisms.

Overview

Life Support

Clinical Effects

0.2.1)

A) USES: Penicillins are used to treat gram-negative bacilli that can include second-generation (eg, ampicillin, amoxicillin), third-generation (eg, carbenicillin and ticarcillin), and fourth-generation penicillins (eg, piperacillin).
B) PHARMACOLOGY: Penicillin is derived from the fungus penicillum. As a class, penicillins contain a 6 aminopenicillanic acid nucleus, composed of a beta-lactam ring fused to a 5 member thiazolidine ring. Penicillins and other beta-lactams inhibit cell wall mucopeptide synthesis.
C) TOXICOLOGY: A penicillin can act as an agonist at the picrotoxin binding site causing GABA antagonism, CNS excitation and seizures. High doses of amoxicillin can cause crystal precipitation in the urine, with hematuria and renal insufficiency.
D) EPIDEMIOLOGY: Penicillin overdose is relatively uncommon, but has the potential to produce severe toxicity.
E) WITH THERAPEUTIC USE

1) ADVERSE EFFECTS: COMMON: GASTROINTESTINAL: Nausea, vomiting, diarrhea, epigastric distress, and black hairy tongue are likely with orally administered penicillins. RENAL: Renal failure, crystalluria, interstitial nephritis, and hemorrhagic cystitis have been reported following the use of penicillin derivatives. Symptoms are frequently associated with sensitivity reactions and may include the following: DERMATOLOGY: Dermatologic reactions can vary greatly in severity, character, and distribution. Amoxicillin and ampicillin appears to cause skin rashes more frequently than other penicillins. HEMATOLOGIC: Thrombocytopenia, neutropenia, and agranulocytosis have occurred following administration of the semisynthetic penicillins and may be related to a hypersensitivity reaction.
2) SEVERE: Anaphylaxis may follow an exposure to any amount of penicillin; severe hypersensitivity reactions may result in anaphylaxis. Parenteral exposures are more likely to cause severe allergic reactions compared to an oral exposure.
3) RARE: Penicillin-induced granulocytopenia is rare and has been associated with high-dose parenteral therapy.

F) WITH POISONING/EXPOSURE

1) MILD TO MODERATE TOXICITY: Nausea, vomiting, abdominal pain and diarrhea may develop with ingestion. Skin rashes and urticaria may develop, especially with amoxicillin and ampicillin ingestions. Hematuria, crystalluria and transient renal insufficiency have been reported after amoxicillin overdose.
2) SEVERE TOXICITY: Agitation, confusion, hallucinations, stupor, coma, multifocal myoclonus, seizures and encephalopathy may occur following massive doses of IV penicillins (40 to 100 million units/day). Cardiac arrest and death have been associated with inadvertent intravenous administration of penicillin G (benzathine and procaine). Hyperkalemia may also develop.

0.2.20)

A) Penicillins are classified as FDA pregnancy category B. The amoxicillin/clarithromycin/lansoprazole and amoxicillin/clarithromycin/omeprazole oral combinations are classified as FDA pregnancy category C. Although penicillins most likely cross the placenta in small amounts, human experience with penicillins during pregnancy has not shown any adverse effects to the fetus. In addition, penicillins probably cross into breast milk in low concentrations, but this should not contraindicate breast feeding in the absence of hypersensitivity.

Laboratory Monitoring

Treatment Overview

0.4.2)

A) MANAGEMENT OF MILD TO MODERATE TOXICITY

1) Treatment is symptomatic and supportive. Treat significant vomiting and diarrhea with IV fluids; administer antiemetics, as needed. HYPERSENSITIVITY REACTION: Administer antihistamines, with or without inhaled beta agonists, corticosteroids or epinephrine.

B) MANAGEMENT OF SEVERE TOXICITY

1) ANAPHYLAXIS: Acute anaphylaxis is more likely to occur after parenteral exposure, but may develop with all routes. Administer oxygen, aggressive airway management, antihistamines, epinephrine, corticosteroids, ECG monitoring, and IV fluids. Dysrhythmias should be treated with standard antiarrhythmic drugs, if necessary. SEIZURES: Initially treat with IV benzodiazepines.

C) DECONTAMINATION

1) PREHOSPITAL: Gastric decontamination is unlikely to be necessary.
2) HOSPITAL: Activated charcoal unlikely to be necessary unless toxic coingestants are involved.

D) AIRWAY MANAGEMENT

1) Airway management is unlikely following overdose; however, aggressive airway management is indicated in patients that develop a significant hypersensitivity/anaphylactoid reaction.

E) ANTIDOTE

1) There is no known antidote.

F) INTRATHECAL INJECTION

1) Intrathecal injection has occurred rarely with penicillins. Treat seizures aggressively (benzodiazepines, barbiturates, propofol). Cerebrospinal fluid (CSF) drainage and CSF exchange may be useful after a large overdose. The following information is derived from limited case reports and experience with antineoplastic agents. Keep the patient upright if possible. Immediately drain at least 20 mL CSF; drainage of up to 70 mL has been tolerated in adults. Follow with CSF exchange (remove serial 20 mL aliquots CSF and replace with equivalent volumes of warmed, preservative free normal saline or lactated ringers). Consult a neurosurgeon for placement of a ventricular catheter and begin ventriculolumbar perfusion (infuse warmed preservative free normal saline or LR through ventricular catheter, drain fluid from lumbar catheter; typical volumes 80 to 150 mL/hr for 18 to 24 hours). Dexamethasone 4 mg IV every 6 hours to prevent arachnoiditis.

G) PATIENT DISPOSITION

1) HOME CRITERIA: Asymptomatic children with inadvertent ingestions of pediatric preparations can generally be managed at home. A small number of children ingesting more than 250 mg/kg of amoxicillin have developed crystalluria, hematuria and transient renal insufficiency; any patient who develops urinary symptoms should be referred to a healthcare facility.
2) OBSERVATION CRITERIA: Patients with deliberate overdose, or with more than mild symptoms should be evaluated in a health care facility. All patients with a history of penicillin allergy or evidence of a hypersensitivity reaction should be referred immediately to a healthcare facility. Patients should be observed until symptoms resolve and clinical parameters (eg, vital signs, mental status) are within normal limits.
3) ADMISSION CRITERIA: All patients with symptoms thought related to a penicillin exposure (other than minor diarrhea, stomach upset), and all patients with a history of hypersensitivity reactions to penicillins, should likely be evaluated at a health care facility. Patients with ongoing symptoms should be admitted.
4) CONSULT CRITERIA: Consult a poison center or medical toxicologist for assistance in patients with persistent renal or cardiovascular symptoms.

H) PHARMACOKINETICS

1) SELECT AGENTS: AMOXICILLIN: Approximately, 25% bound to plasma proteins. Half-life after oral administration is 1.3 hours. Amoxicillin is approximately 50% to 70% excreted unchanged in the urine during the first 6 hours after a single 250 mg or 500 mg tablet. AMPICILLIN: Least protein bound (approximately 20%) of all penicillins. Excreted largely unchanged in the urine. PENICILLIN G BENZATHINE and PENICILLIN G PROCAINE: Low solubility; results in slow release from intramuscular injection sites. Slower absorption can result in prolonged serum levels. Peak concentrations usually occur within 3 hours. Approximately, 60% of PCN G is bound to serum protein; widely distributed throughout the body tissues. The drug is excreted rapidly by tubular excretion in patients with normal kidney function. PENICILLIN G SODIUM: Peak serum concentrations are attained immediately after completion of an infusion. The serum half-life via the IV route in healthy adults is 42 minutes (range: 31 to 50 minutes), infants (14 days of age or older) 1.4 hours, and newborns (less than 0 to 6 days) 3.2 hours. Clearance is predominantly via the kidney. TICARCILLIN: Approximately, 45% bound to serum proteins. There is an inverse relationship between the serum half-life and creatinine clearance; half-life approximately 1.1 hours in healthy patients.

I) PREDISPOSING CONDITIONS

1) Underlying renal impairment; hepatic insufficiency.

J) DIFFERENTIAL DIAGNOSIS

1) A history of a previous hypersensitivity reaction to therapeutic penicillin.

0.4.6)

A) INTRATHECAL OVERDOSE

1) Intrathecal injection has occurred rarely with penicillins. Treat seizures aggressively (benzodiapzepines, barbiturates, propofol). Cerebrospinal fluid (CSF) drainage and CSF exchange may be useful after a large overdose. The following information is derived from limited case reports and experience with antineoplastic agents. Keep the patient upright if possible. Immediately drain at least 20 ml CSF; drainage of up to 70 ml has been tolerated in adults. Follow with CSF exchange (remove serial 20 ml aliquots CSF and replace with equivalent volumes of warmed, preservative free normal saline or lactated ringers). Consult a neurosurgeon for placement of a ventricular catheter and begin ventriculolumbar perfusion (infuse warmed preservative free normal saline or LR through ventricular catheter, drain fluid from lumbar catheter; typical volumes 80 to 150 mL/hr for 18 to 24 hours). Dexamethasone 4 mg intravenously every 6 hours to prevent arachnoiditis.

Range Of Toxicity

Clinical Effects

Summary Of Exposure

Vital Signs

3.3.3)

A) WITH THERAPEUTIC USE

1) HYPOTHERMIA

a) CASE REPORT: A rectal temperature of 35.1 degrees C was recorded in a 45-year-old man after beginning treatment with phenoxymethyl penicillin, 600 mg 4 times daily. Discontinuation of the penicillin caused the patient's rectal temperature to rise from 35.1 to 36.8 degrees C (Hassel, 1992).

Heent

3.4.5)

A) WITH POISONING/EXPOSURE

1) RHINITIS

a) CASE REPORT: Rhinitis occurred in a 28-year-old man following an occupational exposure to powdered antibiotics, including piperacillin and cefuroxime. Skin prick tests with both drugs were positive for piperacillin only. A specific inhalational challenge with piperacillin produced immediate rhinitis symptoms (Moscato et al, 1995).

Cardiovascular

3.5.2)

A) CARDIAC ARREST

1) WITH THERAPEUTIC USE

a) Inadvertent intravenous administration of penicillin G has been associated with cardiac arrest and death (Prod Info BICILLIN CR (R) suspension for IM injection, 2009).
b) Rapid intravenous administration of penicillin G potassium can raise serum potassium levels, which may alter cardiac conduction in pacemaker fibers, resulting in cardiac dysrhythmias and cardiopulmonary arrest (Stumpf, 1987).
c) Cardiorespiratory arrest with slow idioventricular rhythm may follow inadvertent IV infusion of procaine penicillin G, probably as a combined result of direct procaine toxicity and microembolization (Galpin et al, 1974).

B) MYOCARDITIS

1) WITH THERAPEUTIC USE

a) CASE REPORT: Hypersensitivity myocarditis was reported in a 13-year-old boy following ampicillin therapy. Cardiac function improved with oxygen therapy, diuretics, dopamine, and methylprednisolone and discontinuation of ampicillin (Garty et al, 1994).

2) WITH POISONING/EXPOSURE

a) CASE REPORT: Fatal hypersensitivity myocarditis was reported in an 11-month-old girl who repeatedly consumed dry cat food. The cat food was found to have a penicillin activity of 31.9 mcg/g. The maximum limit set by FDA for human food is 0.05 mcg/g (Markus et al, 1989).

C) INJURY OF BLOOD VESSEL

1) WITH POISONING/EXPOSURE

a) Vascular injury often follows an unintentional intra-arterial injection of procaine penicillin (Weir, 1988).

Respiratory

3.6.2)

A) RESPIRATORY DISTRESS

1) WITH THERAPEUTIC USE

a) Respiratory distress, including asthma, may develop as a result of a hypersensitivity reaction (Moller et al, 1990; Moscato et al, 1995).

Neurologic

3.7.2)

A) CENTRAL NERVOUS SYSTEM FINDING

1) WITH POISONING/EXPOSURE

a) SUMMARY: Neurotoxic reactions can develop with very high doses of penicillins (Prod Info TIMENTIN(R) IV injection, 2010; Prod Info penicillin G sodium IV, IM injection, 2009).
b) Agitation, confusion, hallucinations, stupor, coma multifocal myoclonus, seizures and encephalopathy may occur following massive doses of IV penicillins (40 to 100 million units/day); patients with renal impairment may be at increased risk (Prod Info penicillin G sodium IV, IM injection, 2009).
c) Hyperactivity or drowsiness have been observed following overdosage of oral amoxicillin/clavulanate (Prod Info AUGMENTIN(R) oral tablets, 2011).

B) SEIZURE

1) WITH THERAPEUTIC USE

a) IMPAIRED RENAL FUNCTION: Neurologic toxicity following parenteral administration of penicillin has occurred in patients with impaired renal function. Generalized tonic-clonic seizures occurred in 2 women with compromised renal function while receiving ampicillin IV; clindamycin, moxalactam, and lidocaine were also being given to this patient (Hodgman et al, 1984).
b) CASE REPORT: Weinstein et al (1964) reported a patient who developed seizures with serum penicillin concentrations of 737 units (433 mcg/mL) 2 hours after IV administration of 10 million units (6 g) (Weinstein et al, 1964).
c) NEONATES: Seizures may occur in very-low-birth-weight (VLBW) neonates (neonates weighing less than 750 g) who receive ampicillin at doses of 25 to 100 mg/kg/dose every 8 to 12 hours. Other factors in these patients that may contribute to the development of seizures include renal impairment and increased permeability of the blood-brain barrier (Shaffer et al, 1998).

C) COMA

1) WITH THERAPEUTIC USE

a) IMPAIRED RENAL FUNCTION: Drowsiness, coma, and generalized muscle twitching after penicillin administration have been reported (Wickerts et al, 1980).

D) PSYCHOTIC DISORDER

1) WITH THERAPEUTIC USE

a) HOIGNE'S SYNDROME

1) SUMMARY: Severe agitation with confusion and accompanying symptoms such as a fear of impending death (Hoigne's syndrome) and visual and auditory hallucinations has been reported in patients receiving parenteral penicillin G benzathine, and less commonly after injection of penicillin G benzathine in combination with penicillin G procaine (Prod Info BICILLIN CR (R) suspension for IM injection, 2009). Hoigne syndrome has also been associated with oral administration of amoxicillin.

a) SIGNS/SYMPTOMS: Imminent fear of death with auditory or visual hallucinations, anxiety, vertigo, tinnitus, neuromuscular twitching, confusion, agitation, depression, seizures, combativeness, tachycardia, hypertension, and abnormal taste (Silber & D'Angelo, 1985; Kraus & Green, 1976; Malone et al, 1988) (Stell & Ojo, 1996).
b) ONSET: Immediate; usually lasting 15 to 60 minutes (Silber & D'Angelo, 1985; Kraus & Green, 1976; Malone et al, 1988).
c) INCIDENCE: 0.3% to 1.7% of procaine penicillin G-treated patients (Utely et al, 1966; Kryst & Wanyura, 1979). It is 6 times more common in men than in women; patients with psychiatric disorders may be at higher risk (Silber & D'Angelo, 1985; Downham & Ramos, 1974).
d) MECHANISM: Attributed to a sudden increase in free procaine levels in the CNS, but also postulated to be related to microemboli formed from penicillin G procaine crystals (Utely et al, 1966; Green et al, 1974; Galpin et al, 1974; Lankin et al, 1983; Weir, 1988).

E) PSYCHOMOTOR AGITATION

1) WITH THERAPEUTIC USE

a) Severe agitation with confusion and accompanying symptoms such as a fear of impending death (Hoigne's syndrome) and visual and auditory hallucinations has been reported in patients receiving parenteral penicillin G benzathine, and less commonly after injection of penicillin G benzathine in combination with penicillin G procaine (Prod Info BICILLIN CR (R) suspension for IM injection, 2009).

F) ASEPTIC MENINGITIS

1) WITH THERAPEUTIC USE

a) CASE REPORT: A 72-year-old man experienced photophobia, lethargy, and mental status changes shortly after completing amoxicillin therapy, 500 mg 3 times daily for 4 days, to treat a sore throat. CSF analysis showed an elevated WBC count, a RBC count of 20, a protein of 97, and a glucose of 76, sterile cultures, and a MRI revealed mild meningeal enhancement. The patient recovered with supportive care (Wittmann & Wooten, 2001). Previous medical records of the patient showed that he had experienced 3 episodes during the past 4 years with the onset of similar neurologic symptoms and sterile CSF pleocytosis, 4 to 7 days after beginning amoxicillin therapy, 500 mg 3 times daily, for treatment of upper respiratory infections.

Gastrointestinal

3.8.2)

A) NAUSEA, VOMITING AND DIARRHEA

1) WITH THERAPEUTIC USE

a) The most frequent adverse reactions of orally administered penicillins are nausea, vomiting, diarrhea, epigastric distress, and black hairy tongue (Prod Info AUGMENTIN(R) oral tablets, 2011; Prod Info ampicillin IM, IV injection, 2009). Diarrhea and epigastric distress are dose-related in incidence and severity (Kramer et al, 1985; Alanis & Weinstein, 1983).

2) WITH POISONING/EXPOSURE

a) Gastrointestinal symptoms, including stomach and abdominal pain, vomiting and diarrhea are likely to occur following overdose of amoxicillin/clavulanate (Prod Info AUGMENTIN(R) oral tablets, 2011).

Hepatic

3.9.2)

A) LIVER ENZYMES ABNORMAL

1) WITH THERAPEUTIC USE

a) SUMMARY: An elevation in serum liver enzymes (ie, aspartate aminotransferase (SGOT), alanine aminotransferase (SGPT), alkaline phosphatase, BUN, LDH, and serum bilirubin) have been observed with some penicillin therapies (Prod Info AUGMENTIN(R) oral tablets, 2011; Prod Info TIMENTIN(R) IV injection, 2010; Prod Info BICILLIN CR (R) suspension for IM injection, 2009).
b) CASE REPORT: A 67-year-old woman presented to the ED with abdominal pain, nausea, fatigue, anorexia, night sweats, and elevated liver enzymes 15 days after beginning penicillin V therapy, 250 mg orally 3 times daily. Liver enzymes normalized a few days after therapy was discontinued (Onate et al, 1995).
c) CASE REPORT: A 67-year-old man developed hepatotoxicity after ingesting 16 amoxicillin/clavulanic acid tablets, over a 6-day period, to treat an upper respiratory tract infection. The patient's liver enzymes gradually normalized after 6 weeks. Three months later, the patient was treated with erythromycin ethylsuccinate for another upper respiratory tract infection and subsequently developed hepatotoxicity again, including elevated liver enzymes. The liver enzymes normalized after discontinuation of the antibiotic. The authors suggested that in patients with previously documented amoxicillin/clavulanic acid liver toxicity, erythromycin should be administered with caution based on the possible existence of a common metabolic pathway for both drugs (Horsmans & Geubel, 1994).

B) CHOLESTATIC HEPATITIS

1) WITH THERAPEUTIC USE

a) Cholestatic hepatitis has been reported following the administration of amoxicillin/clavulanic acid, cloxacillin, dicloxacillin, flucloxacillin, nafcillin, penicillin, and ticarcillin/potassium clavulanate (Anon, 1992; Decker et al, 1992; Larrey et al, 1992; Olsson et al, 1992; Ryan & Dudley, 1992; Mazuryk et al, 1993; Siegmund & Tarshis, 1993; Lotric-Furlan et al, 1994; Presti et al, 1996; McNeece, 1996; Vial et al, 1997). In most cases, the cholestasis was reversible upon discontinuation of the antibiotic.

C) INFLAMMATORY DISEASE OF LIVER

1) WITH THERAPEUTIC USE

a) CASE REPORT: Granulomatous hepatitis occurred in a patient following oral amoxicillin/clavulanic acid therapy, 1.5 g daily for 14 days. The patient developed jaundice, and his liver enzymes were elevated. A liver biopsy revealed multiple granulomas. After beginning intravenous treatment with mezlocillin and amikacin, followed by oral treatment with norfloxacin, the patient's jaundice gradually disappeared and his liver enzymes normalized (Silvain et al, 1992).

D) ABNORMAL LIVER FUNCTION

1) WITH THERAPEUTIC USE

a) Davies et al (1994) reported 2 cases of acute vanishing bile duct syndrome that occurred following amoxicillin and flucloxacillin therapies. Biopsies, in both patients, showed prolonged cholestasis accompanied by acute ductopenia (Davies et al, 1994).

E) HEPATIC FAILURE

1) WITH THERAPEUTIC USE

a) CASE REPORT: Hepatic and renal failure with progression to Stevens-Johnson syndrome occurred in a 37-year-old man following a 10-day course of amoxicillin/clavulanate therapy. Despite supportive care, the patient developed bacteremia, sepsis, and multiorgan failure, and died approximately 10 weeks later (Limauro et al, 1999).
b) CASE REPORTS: Hepatic failure was reported in 2 patients 4 to 5 days after beginning amoxicillin/clavulanic acid therapy, 625 mg twice daily. Both patients experienced severe jaundice, hepatomegaly, and elevated liver enzymes. Liver biopsies showed centrilobular cholestasis and hydropic degeneration. One patient recovered following supportive treatment; however, the other patient developed thrombotic thrombocytopenic purpura, continued to deteriorate despite aggressive supportive therapy, and died due to multiorgan system failure (Ersoz et al, 2001).

Genitourinary

3.10.2)

A) ACUTE RENAL FAILURE SYNDROME

1) WITH POISONING/EXPOSURE

a) ACUTE TOXICITY

1) Acute oliguric renal failure has been described in a 3-year-old boy who ingested amoxicillin 574 mg/kg (Geller et al, 1986).
2) Jones et al (1993) reported 2 cases of acute oliguric renal failure occurring in 2 children following overdose ingestions of amoxicillin. The clinical symptoms resolved within 3 days. In the first case, a 7-year-old boy ingested a total of 6 g of amoxicillin and presented with hematuria, oliguria, and vomiting. In the other case, a 2.5-year-old toddler ingested a total dose of 7.5 to 12 g of amoxicillin. Twenty-four hours later, he presented with abdominal cramps, vomiting, lethargy, and dysuria (Jones et al, 1993):
3) A 5-year-old boy developed nonoliguric acute renal failure after ingesting amoxicillin 3.75 g. The patient developed hematuria, dysuria, and abdominal pain. The symptoms resolved 5 days later (Belko et al, 1995).

b) CYSTITIS HEMORRHAGIC

1) CASE REPORT: Gross hematuria, with no evidence of renal dysfunction, was reported in a 3-year-old boy who ingested 333 to 733 mg/kg of amoxicillin. Hematuria was present 3 hours after ingestion and cleared within 24 hours (Bright et al, 1989).

c) CRYSTALLURIA

1) The manufacturer has reported the occurrence of crystalluria, progressing to renal failure in some instances, in adult and pediatric patients following overdoses with amoxicillin (Prod Info Augmentin, 2004).
2) CASE REPORT: A 45-year-old woman was treated with amoxicillin 2 g 3 times daily for pneumonia and became anuric with severe bilateral lumbar pain 12 days after starting therapy. Therapy was stopped. Clinical signs included a rising serum creatinine (6.7 mg/dL) and a small amount of red urine that contained many crystals. Infrared spectrophotometry confirmed that the crystals were trihydrated amoxicillin. Symptoms resolved completely within 6 days, with no permanent sequelae (Labriola et al, 2003).
3) Another patient developed crystalluria after 2 days of therapy with oral amoxicillin. Infrared spectroscopy confirmed the presence of pure amoxicillin trihydrate. No change in renal function occurred. Transient crystalluria resolved with the discontinuation of therapy (Fogazzi et al, 2003).
4) CASE REPORT: A 2-year-old boy ingested approximately 6.375 g (580 mg/kg) of amoxicillin suspension and presented to the emergency department (ED)1.5 hours later with crystalluria. The patient recovered following intravenous saline administration (Selzer & Roberts, 1997).

B) ABNORMAL RENAL FUNCTION

1) WITH THERAPEUTIC USE

a) ELEVATED CREATININE

1) Creatinine may be elevated during therapy (Prod Info TIMENTIN(R) IV injection, 2010; Prod Info BICILLIN CR (R) suspension for IM injection, 2009)

b) NEPHRITIS INTERSTITIAL

1) Acute interstitial nephritis has been reported following cloxacillin, methicillin, nafcillin, and piperacillin use. The symptoms gradually resolved following discontinuation of the antibiotic (Appel, 1980) (Ortiz-Garcia et al, 1992) (Guharoy et al, 1993; Soto et al, 1993; Pill et al, 1997). Interstitial nephritis and hematuria have also been reported rarely with amoxicillin therapy (Prod Info AUGMENTIN(R) oral tablets, 2011).
2) CASE REPORT: A 4-year-old boy developed reversible acute tubulointerstitial nephritis following an inadvertent overdose of 240 mg/kg of amoxicillin. Difficulty passing urine and gross hematuria occurred within 2 hours of overdose; the patient recovered completely with supportive care (Schellie & Groshong, 1999).

c) RENAL FAILURE

1) CASE REPORT: A 37-year-old man developed renal failure, with peak BUN and creatinine levels of 86 mg/dL and 6.9 mg/dL, respectively, approximately 2 months after beginning a 10-day course of amoxicillin/clavulanate therapy. The patient also developed hepatic failure and Stevens-Johnson syndrome with his condition deteriorating to bacteremia, sepsis, and multiorgan failure resulting in death approximately 10 weeks after beginning the amoxicillin treatment (Limauro et al, 1999).

3.10.3)

A) ANIMAL STUDIES

1) RENAL FAILURE

a) Pascoe et al (1994) reported that, during a 1.5 year period, 7 dogs were given nafcillin during surgery, for antimicrobial prophylaxis, and subsequently developed postoperative renal failure. Six of the 7 dogs responded to fluid therapy and 1 dog was euthanized due to the severity and unresponsiveness of the renal failure (Pascoe et al, 1994).

Hematologic

3.13.2)

A) BLOOD COAGULATION PATHWAY FINDING

1) WITH THERAPEUTIC USE

a) SUMMARY: Anemia, eosinophilia, leukopenia, neutropenia, thrombocytopenia, prolonged PT and bleeding time and agranulocytosis have been observed during therapy with penicillins (Prod Info TIMENTIN(R) IV injection, 2010; Prod Info penicillin G sodium IV, IM injection, 2009; Prod Info ampicillin IM, IV injection, 2009).
b) Prolonged INR, thrombocytopenia, and coagulopathies associated with a qualitative platelet defect and aggregation abnormalities have been reported following IV therapy with penicillin G in a dose of 12 million units/day (Roberts, 1974).
c) Coagulopathies occurred following intravenous treatment of piperacillin in 2 children with cystic fibrosis. Both patients developed a serum sickness-like illness (fevers, rashes, and abnormal liver enzymes) within 3 weeks of piperacillin therapy. Coagulopathies included thrombocytopenia, prolonged INR and PTT, decreased fibrinogen, and elevated levels of fibrin degradation products. Both the serum sickness-like illness and coagulopathy resolved after discontinuation of piperacillin (Rye et al, 1994).

B) THROMBOCYTOPENIC DISORDER

1) WITH THERAPEUTIC USE

a) Thrombocytopenia has developed during therapy with penicillins (eg, amoxicillin/clavulanate, mezlocillin, penicillin G and piperacillin) (Prod Info AUGMENTIN(R) oral tablets, 2011; Prod Info ampicillin IM, IV injection, 2009; Prod Info BICILLIN CR (R) suspension for IM injection, 2009). The platelet counts normalized after discontinuation of the antibiotics (Olivera et al, 1992; Gharpure et al, 1993).

C) LEUKOPENIA

1) WITH THERAPEUTIC USE

a) A 12-year-old boy developed neutropenia 20 days after beginning nafcillin therapy, 750 mg IV every 4 hours. Nine days after the nafcillin was discontinued, the patient's WBC normalized (Walbroehl & John, 1992).
b) Laboratory tests revealed severe neutropenia in a 29-year-old man given piperacillin/tazobactam for 17 days. Drug therapies were discontinued and the WBC and neutrophil counts progressively increased to normal values (Burken et al, 1995).

D) AGRANULOCYTOSIS

1) WITH THERAPEUTIC USE

a) Leung et al (1995) reported agranulocytosis in a 37-year-old man following intravenous cloxacillin and netilmicin therapy, with a total cloxacillin dose of 165 g. The agranulocytosis gradually resolved following discontinuation of both antibiotics (Leung et al, 1995).

Dermatologic

3.14.2)

A) ERUPTION

1) WITH THERAPEUTIC USE

a) Dermatologic reactions vary greatly in severity, character, and distribution. Amoxicillin and ampicillin appear to cause skin rashes more frequently than other penicillins (Gross et al, 1992; Garty et al, 1994; Jay et al, 1994; Arias et al, 1995; Dhar & Kanwar, 1995; Lim & Ng, 1995; Adcock & Rodman, 1996; Marra & Shalansky, 1996). Symptoms resolved upon discontinuation of the antibiotics.
b) Four patients with delayed allergic skin reactions to amoxicillin or ampicillin were able to tolerate benzyl penicillin and phenoxymethyl penicillin. The presence of certain side chains in ampicillin and amoxicillin may make them more common inducers of allergic reactions (Vega et al, 1994).
c) CASE REPORT: A 28-year-old man developed a cutaneous rash after occupational exposure with cefuroxime sodium and piperacillin sodium. A skin prick test with piperacillin sodium was strongly positive. After a rechallenge with piperacillin, the patient again experienced a cutaneous rash, confirming that the rash was caused by the occupational exposure to piperacillin (Moscato et al, 1995).

B) STEVENS-JOHNSON SYNDROME

1) WITH THERAPEUTIC USE

a) Stevens-Johnson syndrome may develop as a result of a hypersensitivity reaction to some penicillins (Prod Info TIMENTIN(R) IV injection, 2010).
b) The Committee on Safety of Medicines in the UK has received 5 reports of Stevens-Johnson syndrome associated with amoxicillin (Davidson & Windebank, 1986).
c) CASE REPORT: Stevens-Johnson syndrome developed in a 37-year-old man approximately 2 months after beginning a 10-day course of amoxicillin/clavulanate therapy. Despite supportive treatment, the patient died approximately 2 weeks later due to bacteremia, sepsis, and multiorgan failure (Limauro et al, 1999).

C) CONTACT DERMATITIS

1) WITH THERAPEUTIC USE

a) CASE REPORT: Systemic allergic contact dermatitis occurred in a 60-year-old woman following ingestion of amoxicillin 1000 mg for 10 days. A closed patch test with amoxicillin was strongly positive. The rash disappeared within 3 days after discontinuation of amoxicillin. The rash was referred to as a "baboon syndrome" due to its appearance on the buttocks and the upper inner surface of the thigh (Duve et al, 1994).

2) WITH POISONING/EXPOSURE

a) CASE SERIES: Fifty-six workers in 1 Danish pharmaceutical factory developed reactions including contact dermatitis, hay fever, and asthma within 3 months of airborne exposure to pivampicillin (Moller et al, 1990).
b) OCCUPATIONAL EXPOSURE: Medical workers, such as nurses and veterinarians, may develop contact sensitivity from repeated exposure to penicillins; over-the-counter penicillin is still available in parts of the world. Urticarial anaphylaxis may occur in these sensitive populations when oral penicillin is administered (Rietschel, 1994).
c) CASE REPORT: A 48-year-old nurse with a known history of penicillin allergy developed contact dermatitis after unintentionally being sprayed in the face with a small amount of penicillin while giving an injection (Pecegueiro, 1990).

D) TISSUE NECROSIS

1) WITH POISONING/EXPOSURE

a) Cyanosis and swelling occurred in two young children as the result of inadvertent intra-arterial injection of penicillin G (Schanzer et al, 1979).
b) Incomplete cauda equina lesions with ischemia and necrosis over the buttocks occurred when benzathine penicillin was inadvertently injected intra-arterially in a 12-year-old patient. It was suggested that the anterolateral aspect of the thigh is a preferable injection site in infants and children, using a short needle (2.5 cm) and held at an angle out of proximity of major vessels (Meyer et al, 1981).

E) INJECTION SITE REACTION

1) WITH THERAPEUTIC USE

a) Injection site reactions including pain, burning, swelling, induration, inflammation, abscess, necrosis, cellulitis, and skin ulcer may develop with parenteral therapy (Prod Info TIMENTIN(R) IV injection, 2010; Prod Info penicillin G sodium IV, IM injection, 2009; Prod Info BICILLIN CR (R) suspension for IM injection, 2009). Neurovascular reactions (ie, warmth, vasospasm, pallor, numbness and/or cyanosis of the extremity, and neurovascular damage) may also occur with therapy (Prod Info BICILLIN CR (R) suspension for IM injection, 2009).

Immunologic

3.19.2)

A) CELL-MEDIATED IMMUNE REACTION

1) WITH THERAPEUTIC USE

a) SUMMARY: Penicillins are frequently associated with hypersensitivity reactions. Patients may be hypersensitive to natural penicillins, semisynthetic penicillins, or both (Prod Info AUGMENTIN(R) oral tablets, 2011; Prod Info TIMENTIN(R) IV injection, 2010; Prod Info penicillin G sodium IV, IM injection, 2009; Prod Info BICILLIN CR (R) suspension for IM injection, 2009; Prod Info ampicillin IM, IV injection, 2009; Rudzki & Rebandel, 1991; Warrington et al, 1993; Vega et al, 1994).

1) The allergic reaction ranges from a mild rash to fatal anaphylaxis. Allergic reactions may occur almost immediately or may be delayed in onset for 72 hours or longer.
2) Although the more serious reactions tend to occur following parenteral administration, anaphylaxis has followed oral doses and intradermal skin testing. Fever or eosinophilia may occasionally be the only signs of hypersensitivity.

b) SENSITIZATION: Most reactions appear in people previously exposed to penicillins; however, reactions may occur during an extended first course of these drugs.
c) Inapparent sources of exposure, including penicillin residues in foods and breast milk from a mother treated with penicillin, may precede a reaction to therapeutic use (Weiss & Adkinson, 1988).
d) In a study, conducted by Torres et al (1996), it was determined that oral cloxacillin induced a selective allergic reaction, whereas parenteral cloxacillin did not. Because other penicillins, given both orally and parenterally, were shown to be well tolerated, it is postulated that the oral cloxacillin formed a structure produced by the pH conditions of the gastric barrier, thus causing a selective allergic reaction.
e) CROSS-REACTION

1) Patients with signs attributable to sensitivity to penicillin-family antibiotics may test positive in patch tests to other antibiotics such as amoxicillin-clavulanic acid (Kennedy et al, 1989).
2) IMIPENEM: Ten of 20 subjects who tested positive to penicillin on an in vivo skin test also reacted to imipenem (Saxon et al, 1988).

a) Extensive in vivo cross-reactivity to the penicillins has been seen with the bicyclic carbapenem beta-lactam drugs, including imipenem (Saxon et al, 1988).

f) HEMOLYSIS

1) Other hypersensitivity reactions include development of a positive Coombs test, resulting in hemolytic anemia; this reaction usually occurs only following large intravenous doses of penicillin G or carbenicillin disodium.

B) ANAPHYLACTOID REACTION

1) WITH THERAPEUTIC USE

a) SUMMARY

1) Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have occurred in some patients receiving penicillin therapy (Prod Info penicillin G sodium IV, IM injection, 2009). It is more likely to occur following parenteral therapy, but it has occurred in patients receiving oral penicillins (Prod Info BICILLIN CR (R) suspension for IM injection, 2009; Prod Info ampicillin IM, IV injection, 2009).

b) ORAL THERAPY

1) Severe anaphylaxis developed in 2 patients within minutes of oral ingestion of penicillin V and talampicillin (Simmonds et al, 1978).
2) The incidence of fatal anaphylactic reactions to oral penicillin was 6% of total anaphylactic cases in 1 review of 151 anaphylactic fatalities (Idsoe et al, 1968).
3) In a study conducted by Vega et al (1994), 37 of 54 patients (69%) with immediate allergies to amoxicillin developed anaphylaxis (Vega et al, 1994).

c) WARNING: BETA BLOCKER THERAPY

1) Fatal anaphylaxis was reported in 2 patients on chronic beta-blocker therapy after administration of oral penicillin V.
2) Patients receiving beta-blockers are known to be at a greater risk for serious anaphylactic reactions requiring aggressive therapy (Berkelman et al, 1986).

Reproductive

3.20.1)

3.20.2)

A) LACK OF INFORMATION

1) PENICILLIN G BENZATHINE: There are no adequate and well-controlled studies of penicillin G benzathine use during pregnancy (Prod Info BICILLIN(R)L-A suspension for IM injection, 2006).

B) LACK OF EFFECT

1) Although penicillins most likely cross the placenta in small amounts, human experience with penicillins during pregnancy has not shown any adverse effects to the fetus (Prod Info BICILLIN(R)L-A suspension for IM injection, 2006).

C) ANIMAL STUDIES

1) PENICILLIN G BENZATHINE: In animal studies, there was no evidence of impaired fertility or fetal harm when mice, rats, and rabbits were exposed to penicillin G (Prod Info BICILLIN(R)L-A suspension for IM injection, 2006).
2) PIPERACILLIN/TAZOBACTAM: In animal studies, there was no clear evidence of teratogenicity when mice and rats were given piperacillin/tazobactam at doses 1 and 2 times and 2 and 3 times the maximum recommended human dose (MRHD) on a mg/m(2) basis), respectively. Mice and rats revealed no evidence of fetal harm when administered piperacillin doses up to half the MRHD on a mg/m(2) basis and tazobactam at doses up to 6 and 14 times the human dose on a mg/m(2)) basis, respectively (Prod Info ZOSYN(R) IV injection, 2007).

3.20.3)

A) PREGNANCY CATEGORY

1) Penicillins (amoxicillin, ampicillin, dicloxacillin, nafcillin, oxacillin, penicillin G benzathine, penicillin G benzathine/penicillin G procaine, penicillin G potassium, penicillin G procaine, penicillin V potassium, piperacillin, and ticarcillin) have been classified by the manufacturers as FDA pregnancy category B (Prod Info Bicillin(R) C-R intramuscular injection suspension, 2015; Prod Info AMOXIL(R) oral capsules, tablets, chewable tablets, powder for oral suspension, 2008; Prod Info ampicillin injection, 2004; Prod Info BICILLIN(R)L-A suspension for IM injection, 2006; Prod Info dicloxacillin sodium oral capsules, 2004; Prod Info Nafcillin IV injection, 2007; Prod Info oxacillin IV injection, solution, 2007; Prod Info penicillin G potassium IV injection, 2008; Prod Info penicillin G, procaine IM injection suspension, 2002; Prod Info PIPRACIL(R) injection, 2004).
2) The amoxicillin/clarithromycin/lansoprazole and amoxicillin/clarithromycin/omeprazole oral combinations are classified as FDA pregnancy category C (Prod Info Omeclamox-Pak(TM) oral kit, 2015; Prod Info PREVPAC(TM) oral delayed-release capsules, oral capsules, oral tablets, 2014).

3.20.4)

A) BREAST MILK

1) All penicillins most likely cross into breast milk in low concentrations, but this should not contraindicate breast feeding in the absence of hypersensitivity.
2) Although the clinical significance remains uncertain, potential problems for the nursing infant whose mother is receiving a penicillin include sensitization, modification of bowel flora, and difficulty in the interpretation of culture results (Briggs et al, 1998).
3) PENICILLIN G BENZATHINE: Soluble penicillin G is excreted into human breast milk (Prod Info penicillin G potassium IV injection, 2008).
4) PENICILLIN G BENZATHINE/PENICILLIN G PROCAINE: Soluble penicillin G is known to be excreted into human breast milk. Exercise caution when administering to a lactating woman (Prod Info Bicillin(R) C-R intramuscular injection suspension, 2015).
5) PIPERACILLIN/TAZOBACTAM: Piperacillin is secreted in low concentrations into human breast milk; however, tazobactam concentrations in human milk have not been studied (Prod Info ZOSYN(R) IV injection, 2007).

3.20.5)

A) LACK OF INFORMATION

1) At the time of this review, no human or animal data were available to assess the potential effects on fertility from exposure to this agent (Prod Info penicillin G potassium IV injection, 2008).

B) ANIMAL STUDIES

1) PIPERACILLIN/TAZOBACTAM: Reproductive studies conducted in rats showed no evidence of impaired fertility when administered piperacillin/tazobactam at doses similar to the maximum recommended human daily dose (MRHD) on a mg/m(2)) basis (Prod Info ZOSYN(R) IV injection, 2007).

Laboratory Monitoring

Monitoring Parameters Levels

4.1.1)

A) Monitor vital signs and mental status.
B) Monitor urinalysis, renal function and electrolytes following a significant overdose.
C) Monitor fluid status in patients with severe vomiting and/or diarrhea.
D) Obtain a baseline ECG and institute continuous cardiac monitoring in patients with a significant IV overdose.
E) Plasma concentrations of these antibiotics are not clinically useful in overdose situations.

4.1.2)

A) BLOOD/SERUM CHEMISTRY

1) Monitor renal function and electrolytes following very large doses of penicillins, or when such drugs are used in large doses for prolonged periods of time.
2) Plasma concentrations of these antibiotics are not clinically useful in overdose situations.

4.1.3)

A) URINALYSIS

1) Monitor urinalysis following very large doses of penicillins, or when such drugs are used in large doses for prolonged periods of time.

B) INFRARED SPECTROPHOTOMETRY

1) Infrared spectrophotometry has been used to confirm the presence of amoxicillin (trihydrated amoxicillin) crystals in the urine (Labriola et al, 2003; Fogazzi et al, 2003).

Treatment

Life Support

Patient Disposition

6.3.1)

6.3.1.1) ADMISSION CRITERIA/ORAL

A) Patients with ongoing symptoms should be admitted.

6.3.1.2) HOME CRITERIA/ORAL

A) Asymptomatic children with inadvertent ingestions of pediatric preparations can generally be managed at home.
B) A small number of children ingesting more than 250 mg/kg of amoxicillin have developed crystalluria, hematuria and transient renal insufficiency. If significant symptoms (eg, lethargy, dysuria, hematuria, oliguria, ongoing nausea and vomiting) develop, referral to a healthcare facility is recommended.
C) STUDIES

1) GENERAL: There are limited data regarding the acute toxic dose of penicillin.

a) CASE SERIES: In a prospective study of 61 cases of inadvertent ingestion of penicillin or cephalosporin derivative in children less than 6 years of age, 47 (72.3%) cases involved amoxicillin suspension. Eighty-four percent of the children remained completely asymptomatic without gastric decontamination. Of the 13 children that developed symptoms, 10 cases were due to amoxicillin. The mean dose that produced symptoms was 132.8 mg/kg amoxicillin (range: 31 to 250 mg/kg). Onset of symptoms occurred within 24 hours and resolved within 72 hours. Symptoms were limited to diarrhea, abdominal pain, vomiting, and facial rash in 2 children. The findings suggest that an ingestion of 250 mg/kg or less of a penicillin and/or cephalosporin product is not associated with significant adverse events and does not require gastric decontamination (Swanson-Biearman et al, 1988).
b) In a limited number of cases, crystalluria, hematuria and acute renal failure have developed in children after overdose of amoxicillin.

1) CASE REPORT: A 3-year-old boy developed reversible oliguric acute renal failure after ingesting 574 mg/kg of amoxicillin; symptoms (spontaneous vomiting followed by gross hematuria) developed within 3 hours of ingestion (Geller et al, 1986).
2) CASE REPORTS: Acute renal failure was also reported in 2 children (ages 2.5 and 7 years) after inadvertently ingesting 7.5 to 12 g and 6 g of amoxicillin, respectively. Early symptoms included vomiting, abdominal pain and hematuria. The youngest child became lethargic about 16 hours after exposure. Both recovered completely with supportive care (Jones et al, 1993).

6.3.1.3) CONSULT CRITERIA/ORAL

A) Consult a poison center or medical toxicologist for assistance in patients with persistent renal or cardiovascular symptoms.

6.3.1.5) OBSERVATION CRITERIA/ORAL

A) Patients with deliberate overdose, or with more than mild symptoms should be evaluated in a health care facility. All patients with a history of penicillin allergy or evidence of a hypersensitivity reaction should be referred immediately to a healthcare facility. Patients should be observed until symptoms resolve and clinical parameters (eg, vital signs, mental status) are within normal limits.

Monitoring

Oral Exposure

6.5.1)

A) SUMMARY

1) GI decontamination is generally not indicated.

B) ACTIVATED CHARCOAL

1) PREHOSPITAL ACTIVATED CHARCOAL ADMINISTRATION

a) Consider prehospital administration of activated charcoal as an aqueous slurry in patients with a potentially toxic ingestion who are awake and able to protect their airway. Activated charcoal is most effective when administered within one hour of ingestion. Administration in the prehospital setting has the potential to significantly decrease the time from toxin ingestion to activated charcoal administration, although it has not been shown to affect outcome (Alaspaa et al, 2005; Thakore & Murphy, 2002; Spiller & Rogers, 2002).

1) In patients who are at risk for the abrupt onset of seizures or mental status depression, activated charcoal should not be administered in the prehospital setting, due to the risk of aspiration in the event of spontaneous emesis.
2) The addition of flavoring agents (cola drinks, chocolate milk, cherry syrup) to activated charcoal improves the palatability for children and may facilitate successful administration (Guenther Skokan et al, 2001; Dagnone et al, 2002).

2) CHARCOAL DOSE

a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).

1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).

b) ADVERSE EFFECTS/CONTRAINDICATIONS

1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).

6.5.2)

A) ACTIVATED CHARCOAL

1) Activated charcoal may be indicated in some cases following an extremely large overdose (greater than 15 times the usual single therapeutic dose; for example, ingestions exceeding 250 milligrams/kilogram of amoxicillin).
2) CHARCOAL ADMINISTRATION

a) Consider administration of activated charcoal after a potentially toxic ingestion (Chyka et al, 2005). Administer charcoal as an aqueous slurry; most effective when administered within one hour of ingestion.

3) CHARCOAL DOSE

b) ADVERSE EFFECTS/CONTRAINDICATIONS

6.5.3)

A) SUPPORT

1) Treatment is symptomatic and supportive. Following an ingestion exceeding the usual therapeutic dose, hold further doses until the patient can be evaluated.

B) MONITORING OF PATIENT

1) Monitor vital signs and mental status.
2) Monitor renal function and electrolytes following a significant overdose.
3) Monitor fluid status in patients with severe vomiting and/or diarrhea.
4) Obtain a baseline ECG and institute continuous cardiac monitoring in patients with a significant exposure.
5) Plasma levels of these antibiotics are not clinically useful in overdose situations.

C) ANAPHYLAXIS

1) Monitor for signs and symptoms of hypersensitivity. Anaphylaxis should be managed with establishment of a patent airway, epinephrine, and diphenhydramine.
2) SUMMARY

a) Mild to moderate allergic reactions may be treated with antihistamines with or without inhaled beta adrenergic agonists, corticosteroids or epinephrine. Treatment of severe anaphylaxis also includes oxygen supplementation, aggressive airway management, epinephrine, ECG monitoring, and IV fluids.

3) BRONCHOSPASM

a) ALBUTEROL

1) ADULT: 2.5 to 5 milligrams in 2 to 4.5 milliliters of normal saline delivered per nebulizer every 20 minutes up to 3 doses. If incomplete response administer 2.5 to 10 mg every 1 to 4 hours as needed, or 10 to 15 mg/hr by continuous nebulization as needed (National Heart,Lung,and Blood Institute, 2007). CHILD: 0.15 milligram/kilogram (minimum 2.5 milligrams) per nebulizer every 20 minutes up to 3 doses. If incomplete response administer 0.15 to 0.3 mg/kg (up to 10 mg) every 1 to 4 hours as needed, or 0.5 mg/kg/hr by continuous nebulization (National Heart,Lung,and Blood Institute, 2007).

4) CORTICOSTEROIDS

a) Consider systemic corticosteroids in patients with significant bronchospasm.
b) PREDNISONE: ADULT: 40 to 80 milligrams/day. CHILD: 1 to 2 milligrams/kilogram/day (maximum 60 mg) in 1 to 2 divided doses divided twice daily (National Heart,Lung,and Blood Institute, 2007).

5) MILD CASES

a) DIPHENHYDRAMINE

1) SUMMARY: Oral diphenhydramine, as well as other H1 antihistamines can be used as indicated (Lieberman et al, 2010).
2) ADULT: 50 milligrams orally, or 10 to 50 mg intravenously at a rate not to exceed 25 mg/min or may be given by deep intramuscular injection. A total of 100 mg may be administered if needed. Maximum daily dosage is 400 mg (Prod Info diphenhydramine HCl intravenous injection solution, intramuscular injection solution, 2013).
3) CHILD: 5 mg/kg/24 hours or 150 mg/m(2)/24 hours. Divided into 4 doses, administered intravenously at a rate not exceeding 25 mg/min or by deep intramuscular injection. Maximum daily dosage is 300 mg (Prod Info diphenhydramine HCl intravenous injection solution, intramuscular injection solution, 2013).

6) MODERATE CASES

a) EPINEPHRINE: INJECTABLE SOLUTION: It should be administered early in patients by IM injection. Using a 1:1000 (1 mg/mL) solution of epinephrine. Initial Dose: 0.01 mg/kg intramuscularly with a maximum dose of 0.5 mg in adults and 0.3 mg in children. The dose may be repeated every 5 to 15 minutes, if no clinical improvement. Most patients respond to 1 or 2 doses (Nowak & Macias, 2014).

7) SEVERE CASES

a) EPINEPHRINE

1) INTRAVENOUS BOLUS: ADULT: 1 mg intravenously as a 1:10,000 (0.1 mg/mL) solution; CHILD: 0.01 mL/kg intravenously to a maximum single dose of 1 mg given as a 1:10,000 (0.1 mg/mL) solution. It can be repeated every 3 to 5 minutes as needed. The dose can also be given by the intraosseous route if IV access cannot be established (Lieberman et al, 2015). ALTERNATIVE ROUTE: ENDOTRACHEAL ADMINISTRATION: If IV/IO access is unavailable. DOSE: ADULT: Administer 2 to 2.5 mg of 1:1000 (1 mg/mL) solution diluted in 5 to 10 mL of sterile water via endotracheal tube. CHILD: DOSE: 0.1 mg/kg to a maximum of 2.5 mg administered as a 1:1000 (1 mg/mL) solution diluted in 5 to 10 mL of sterile water via endotracheal tube (Lieberman et al, 2015).
2) INTRAVENOUS INFUSION: Intravenous administration may be considered in patients poorly responsive to IM or SubQ epinephrine. An epinephrine infusion may be prepared by adding 1 mg (1 mL of 1:1000 (1 mg/mL) solution) to 250 mL D5W, yielding a concentration of 4 mcg/mL, and infuse this solution IV at a rate of 1 mcg/min to 10 mcg/min (maximum rate). CHILD: A dosage of 0.01 mg/kg (0.1 mL/kg of a 1:10,000 (0.1 mg/mL) solution up to 10 mcg/min (maximum dose 0.3 mg) is recommended for children (Lieberman et al, 2010). Careful titration of a continuous infusion of IV epinephrine, based on the severity of the reaction, along with a crystalloid infusion can be considered in the treatment of anaphylactic shock. It appears to be a reasonable alternative to IV boluses, if the patient is not in cardiac arrest (Vanden Hoek,TL,et al).

8) AIRWAY MANAGEMENT

a) OXYGEN: 5 to 10 liters/minute via high flow mask.
b) INTUBATION: Perform early if any stridor or signs of airway obstruction.
c) CRICOTHYROTOMY: Use if unable to intubate with complete airway obstruction (Vanden Hoek,TL,et al).
d) BRONCHODILATORS are recommended for mild to severe bronchospasm.
e) ALBUTEROL: ADULT: 2.5 to 5 milligrams in 2 to 4.5 milliliters of normal saline delivered per nebulizer every 20 minutes up to 3 doses. If incomplete response administer 2.5 to 10 mg every 1 to 4 hours as needed, or 10 to 15 mg/hr by continuous nebulization as needed (National Heart,Lung,and Blood Institute, 2007).
f) ALBUTEROL: CHILD: 0.15 milligram/kilogram (minimum 2.5 milligrams) per nebulizer every 20 minutes up to 3 doses. If incomplete response administer 0.15 to 0.3 milligram/kilogram (maximum 10 milligrams) every 1 to 4 hours as needed OR administer 0.5 mg/kg/hr by continuous nebulization (National Heart,Lung,and Blood Institute, 2007).

9) MONITORING

a) CARDIAC MONITOR: All complicated cases.
b) IV ACCESS: Routine in all complicated cases.

10) HYPOTENSION

a) If hypotensive give 500 to 2000 milliliters crystalloid initially (20 milliliters/kilogram in children) and titrate to desired effect (stabilization of vital signs, mentation, urine output); adults may require up to 6 to 10 L/24 hours. Central venous or pulmonary artery pressure monitoring is recommended in patients with persistent hypotension.

1) VASOPRESSORS: Should be used in refractory cases unresponsive to repeated doses of epinephrine and after vigorous intravenous crystalloid rehydration (Lieberman et al, 2010).
2) DOPAMINE: Initial Dose: 2 to 20 micrograms/kilogram/minute intravenously; titrate to maintain systolic blood pressure greater than 90 mm Hg (Lieberman et al, 2010).

11) H1 and H2 ANTIHISTAMINES

a) SUMMARY: Antihistamines are second-line therapy and are used as supportive therapy and should not be used in place of epinephrine (Lieberman et al, 2010).

1) DIPHENHYDRAMINE: ADULT: 25 to 50 milligrams via a slow intravenous infusion or IM. PEDIATRIC: 1 milligram/kilogram via slow intravenous infusion or IM up to 50 mg in children (Lieberman et al, 2010).

b) RANITIDINE: ADULT: 1 mg/kg parenterally; CHILD: 12.5 to 50 mg parenterally. If the intravenous route is used, ranitidine should be infused over 10 to 15 minutes or diluted in 5% dextrose to a volume of 20 mL and injected over 5 minutes (Lieberman et al, 2010).
c) Oral diphenhydramine, as well as other H1 antihistamines, can also be used as indicated (Lieberman et al, 2010).

12) DYSRHYTHMIAS

a) Dysrhythmias and cardiac dysfunction may occur primarily or iatrogenically as a result of pharmacologic treatment (epinephrine) (Vanden Hoek,TL,et al). Monitor and correct serum electrolytes, oxygenation and tissue perfusion. Treat with antiarrhythmic agents as indicated.

13) OTHER THERAPIES

a) There have been a few reports of patients with anaphylaxis, with or without cardiac arrest, that have responded to vasopressin therapy that did not respond to standard therapy. Although there are no randomized controlled trials, other alternative vasoactive therapies (ie, vasopressin, norepinephrine, methoxamine, and metaraminol) may be considered in patients in cardiac arrest secondary to anaphylaxis that do not respond to epinephrine (Vanden Hoek,TL,et al).

14) Based on limited data, cimetidine was reported to be effective in anaphylactic shock refractory to standard therapy (De Soto & Turk, 1989).

D) SEIZURE

1) SUMMARY

a) Attempt initial control with a benzodiazepine (eg, diazepam, lorazepam). If seizures persist or recur, administer phenobarbital or propofol.
b) Monitor for respiratory depression, hypotension, and dysrhythmias. Endotracheal intubation should be performed in patients with persistent seizures.
c) Evaluate for hypoxia, electrolyte disturbances, and hypoglycemia (or, if immediate bedside glucose testing is not available, treat with intravenous dextrose).

2) DIAZEPAM

a) ADULT DOSE: Initially 5 to 10 mg IV, OR 0.15 mg/kg IV up to 10 mg per dose up to a rate of 5 mg/minute; may be repeated every 5 to 20 minutes as needed (Brophy et al, 2012; Prod Info diazepam IM, IV injection, 2008; Manno, 2003).
b) PEDIATRIC DOSE: 0.1 to 0.5 mg/kg IV over 2 to 5 minutes; up to a maximum of 10 mg/dose. May repeat dose every 5 to 10 minutes as needed (Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008).
c) Monitor for hypotension, respiratory depression, and the need for endotracheal intubation. Consider a second agent if seizures persist or recur after repeated doses of diazepam .

3) NO INTRAVENOUS ACCESS

a) DIAZEPAM may be given rectally or intramuscularly (Manno, 2003). RECTAL DOSE: CHILD: Greater than 12 years: 0.2 mg/kg; 6 to 11 years: 0.3 mg/kg; 2 to 5 years: 0.5 mg/kg (Brophy et al, 2012).
b) MIDAZOLAM has been used intramuscularly and intranasally, particularly in children when intravenous access has not been established. ADULT DOSE: 0.2 mg/kg IM, up to a maximum dose of 10 mg (Brophy et al, 2012). PEDIATRIC DOSE: INTRAMUSCULAR: 0.2 mg/kg IM, up to a maximum dose of 7 mg (Chamberlain et al, 1997) OR 10 mg IM (weight greater than 40 kg); 5 mg IM (weight 13 to 40 kg); INTRANASAL: 0.2 to 0.5 mg/kg up to a maximum of 10 mg/dose (Loddenkemper & Goodkin, 2011; Brophy et al, 2012). BUCCAL midazolam, 10 mg, has been used in adolescents and older children (5-years-old or more) to control seizures when intravenous access was not established (Scott et al, 1999).

4) LORAZEPAM

a) MAXIMUM RATE: The rate of intravenous administration of lorazepam should not exceed 2 mg/min (Brophy et al, 2012; Prod Info lorazepam IM, IV injection, 2008).
b) ADULT DOSE: 2 to 4 mg IV initially; repeat every 5 to 10 minutes as needed, if seizures persist (Manno, 2003; Brophy et al, 2012).
c) PEDIATRIC DOSE: 0.05 to 0.1 mg/kg IV over 2 to 5 minutes, up to a maximum of 4 mg/dose; may repeat in 5 to 15 minutes as needed, if seizures continue (Brophy et al, 2012; Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008; Sreenath et al, 2009; Chin et al, 2008).

5) PHENOBARBITAL

a) ADULT LOADING DOSE: 20 mg/kg IV at an infusion rate of 50 to 100 mg/minute IV. An additional 5 to 10 mg/kg dose may be given 10 minutes after loading infusion if seizures persist or recur (Brophy et al, 2012).
b) Patients receiving high doses will require endotracheal intubation and may require vasopressor support (Brophy et al, 2012).
c) PEDIATRIC LOADING DOSE: 20 mg/kg may be given as single or divided application (2 mg/kg/minute in children weighing less than 40 kg up to 100 mg/min in children weighing greater than 40 kg). A plasma concentration of about 20 mg/L will be achieved by this dose (Loddenkemper & Goodkin, 2011).
d) REPEAT PEDIATRIC DOSE: Repeat doses of 5 to 20 mg/kg may be given every 15 to 20 minutes if seizures persist, with cardiorespiratory monitoring (Loddenkemper & Goodkin, 2011).
e) MONITOR: For hypotension, respiratory depression, and the need for endotracheal intubation (Loddenkemper & Goodkin, 2011; Manno, 2003).
f) SERUM CONCENTRATION MONITORING: Monitor serum concentrations over the next 12 to 24 hours. Therapeutic serum concentrations of phenobarbital range from 10 to 40 mcg/mL, although the optimal plasma concentration for some individuals may vary outside this range (Hvidberg & Dam, 1976; Choonara & Rane, 1990; AMA Department of Drugs, 1992).

6) OTHER AGENTS

a) If seizures persist after phenobarbital, propofol or pentobarbital infusion, or neuromuscular paralysis with general anesthesia (isoflurane) and continuous EEG monitoring should be considered (Manno, 2003). Other anticonvulsants can be considered (eg, valproate sodium, levetiracetam, lacosamide, topiramate) if seizures persist or recur; however, there is very little data regarding their use in toxin induced seizures, controlled trials are not available to define the optimal dosage ranges for these agents in status epilepticus (Brophy et al, 2012):

1) VALPROATE SODIUM: ADULT DOSE: An initial dose of 20 to 40 mg/kg IV, at a rate of 3 to 6 mg/kg/minute; may give an additional dose of 20 mg/kg 10 minutes after loading infusion. PEDIATRIC DOSE: 1.5 to 3 mg/kg/minute (Brophy et al, 2012).
2) LEVETIRACETAM: ADULT DOSE: 1000 to 3000 mg IV, at a rate of 2 to 5 mg/kg/min IV. PEDIATRIC DOSE: 20 to 60 mg/kg IV (Brophy et al, 2012; Loddenkemper & Goodkin, 2011).
3) LACOSAMIDE: ADULT DOSE: 200 to 400 mg IV; 200 mg IV over 15 minutes (Brophy et al, 2012). PEDIATRIC DOSE: In one study, median starting doses of 1.3 mg/kg/day and maintenance doses of 4.7 mg/kg/day were used in children 8 years and older (Loddenkemper & Goodkin, 2011).
4) TOPIRAMATE: ADULT DOSE: 200 to 400 mg nasogastric/orally OR 300 to 1600 mg/day orally divided in 2 to 4 times daily (Brophy et al, 2012).

E) VENTRICULAR ARRHYTHMIA

1) Cardiac dysrhythmias should be treated with standard antiarrhythmic drugs, if necessary.

F) BLOOD COAGULATION DISORDER

1) The following protocol has been suggested (Sattler et al, 1986):

a) Hypoprothrombinemia without apparent bleeding: 10 mg vitamin K subQ.
b) Hypoprothrombinemia with bleeding: fresh frozen plasma.
c) Prolonged template bleeding time and bleeding present: platelet transfusions.
d) Prophylaxis: In patients with renal failure, malnutrition, intraabdominal infection, or recent gastrointestinal surgery, administer vitamin K 10 mg parenterally once or twice weekly.

Enhanced Elimination

1) Ampicillin-class antibiotics, amoxicillin and ticarcillin are removed from the circulation by hemodialysis, but as severe toxicity is highly unlikely hemodialysis is almost never indicated.

1) In severe overdosage where increased absorption may have occurred and there exists severe renal impairment, dialysis may be considered for correction of acidosis and electrolytes, rather than for removal of penicillins.

a) Ampicillin-class antibiotics, amoxicillin and ticarcillin are removed from the circulation by hemodialysis (Prod Info AUGMENTIN(R) oral tablets, 2011; Prod Info TIMENTIN(R) IV injection, 2010; Prod Info ampicillin IM, IV injection, 2009).

1) Combined CHARCOAL HEMOPERFUSION and HEMODIALYSIS has been effective in removal of penicillin in a patient with renal failure (Wickerts et al, 1980).

1) PERITONEAL DIALYSIS is of little value in removing excess penicillin (Maher, 1978).
2) In patients with renal failure, ampicillin-class antibiotics cannot be removed from circulation by peritoneal dialysis (Prod Info ampicillin IM, IV injection, 2009).

Abstracts

Case Reports

1) CASE REPORT: A 45-year-old woman treated with 1 tablet of penicillin V went into fatal anaphylactic shock, within 15 minutes of administering the drug, the patient collapsed with cardiac and respiratory arrest. Autopsy revealed cerebral hemorrhage with numerous hyaline thrombi and smaller blood vessels with characteristics of a shock condition. The patient was also found to have pulmonary edema (Bankl & Jellinger, 1968).
2) CASE REPORTS: Kain (1966) described anaphylactic reactions to oral penicillin in 2 patients (Kain, 1966):

a) One patient received 200,000 units of oral potassium penicillin G 4 times daily for 4 days. After the fourth day of therapy, generalized itching developed and red, painful lumps on the feet occurred after the fifth day. The patient developed sudden weakness, respiratory distress, and hypotension. ACTH 40 units IV was administered for 3 days and prednisone 5 mg orally 3 times daily, and the patient completely recovered (Kain, 1966).
b) The second patient received 1 tablet of potassium penicillin G (dose unspecified) and collapsed. Sinus tachycardia was present. Following intense corticosteroid therapy, the patient completely recovered. The authors emphasized that oral penicillin reactions may either occur immediately or be delayed (Kain, 1966).

Range Of Toxicity

Summary

Therapeutic Dose

7.2.1)

A) SPECIFIC SUBSTANCE

1) AMOXICILLIN

a) ORAL: Varies by indication: 250 to 500 mg every 8 hours; 875 mg every 12 hours (Prod Info AMOXIL(R) oral capsules, tablets, powder for oral suspension, 2011).
b) GONORRHEA: ORAL: 3 g as a single oral dose (Prod Info AMOXIL(R) oral capsules, tablets, powder for oral suspension, 2011)

2) AMOXICILLIN/CLARITHROMYCIN/LANSOPRAZOLE

a) The recommended dose is lansoprazole 30 mg combined with amoxicillin 1 g and clarithromycin 500 mg orally twice daily for 10 to 14 days (Prod Info PREVPAC(TM) oral delayed-release capsules, oral capsules, oral tablets, 2014).

3) AMOXICILLIN/CLARITHROMYCIN/OMEPRAZOLE

a) The recommended dose is omeprazole 20 mg combined with amoxicillin 1 g and clarithromycin 500 mg orally twice daily for 10 days (Prod Info Omeclamox-Pak(TM) oral kit, 2015).

4) AMPICILLIN

a) ORAL: 0.25 to 1 g every 6 hours (Prod Info ampicillin oral capsules, suspension, 2011)
b) IM: 500 mg every 4 to 6 hours(Prod Info ampicillin IM, IV injection, 2009)
c) IV: 500 mg every 4 to 6 hours by slow injection over 3 to 5 minutes or by infusion. For serious infections, such as meningitis or endocarditis, 1 to 2 g given over 10 to 15 minutes every 3 to 4 hours(Prod Info ampicillin IM, IV injection, 2009).

5) DICLOXACILLIN

a) ORAL: 125 to 250 mg every 6 hours (Prod Info dicloxacillin sodium oral capsule, 2010)

6) NAFCILLIN

a) IV: 500 mg to 1 g every 4 hours given by slow infusion over 30 to 60 minutes(Prod Info nafcillin IV injection, 2011)

7) OXACILLIN

a) PARENTERAL: 250 mg to 1 g every 4 to 6 hours given by continuous or intermittent IV infusion (Prod Info oxacillin IV injection, 2011).

8) PENICILLIN G BENZATHINE

a) STREPTOCOCCAL: 1.2 million units IM as a single injection (Prod Info BICILLIN (R) L-A suspension for IM injection, 2009)
b) SYPHILIS (EARLY): 2.4 million units IM as a single dose (Prod Info BICILLIN (R) L-A suspension for IM injection, 2009)
c) SYPHILIS (LATE): 2.4 million units IM once weekly for 3 weeks (Prod Info BICILLIN (R) L-A suspension for IM injection, 2009)
d) YAW, BEJEL, and PINTA: 1.2 million units IM in a single dose (Prod Info BICILLIN (R) L-A suspension for IM injection, 2009)

9) PENICILLIN G BENZATHINE/PENICILLIN G PROCAINE

a) BICILLIN(R) C-R

1) PNEUMOCOCCAL INFECTION (EXCLUDING PNEUMOCOCCAL MENINGITIS): The recommended dose is 1,200,000 units IM repeated every 2 or 3 days until temperature is normal for 48 hours (Prod Info Bicillin(R) C-R intramuscular injection suspension, 2015).
2) STREPTOCOCCAL INFECTION: The recommended dose is 2,400,000 units administered via multiple IM sites (Prod Info Bicillin(R) C-R intramuscular injection suspension, 2015)

b) BICILLIN(R) C-R 900/300

1) PNEUMOCOCCAL INFECTION (EXCLUDING PNEUMOCOCCAL MENINGITIS): The recommended dose is 1,200,000 units (penicillin G benzathine 900,000 units/penicillin G procaine 300,000 units) administered by deep IM injection. Repeat every 2 or 3 days until temperature has normalized for 48 hours (Prod Info Bicillin(R) C-R 900/300 intramuscular injection suspension, 2015).
2) STREPTOCOCCAL INFECTION: Group A infection of upper respiratory tract, skin, soft tissue, scarlet fever, or erysipelas, the recommended dose is 1,200,000 units (penicillin G benzathine 900,000 units/penicillin G procaine 300,000 units) administered by deep IM injection (Prod Info Bicillin(R) C-R 900/300 intramuscular injection suspension, 2015).

10) PENICILLIN G POTASSIUM (PARENTERAL)

a) MENINGITIS: 24 million units daily, given as 2 million units every 2 hours by IV infusion(Prod Info penicillin G potassium IV injection, 2008)
b) ERYSIPELOID: 12 to 20 million units/day every 4 to 6 hours for 4 to 6 weeks by IV infusion(Prod Info penicillin G potassium IV injection, 2008)

11) PENICILLIN G PROCAINE

a) IM: 0.3 to 2.4 million units daily (Prod Info penicillin G procaine suspension for IM injection, 2006)

12) PENICILLIN V

a) ORAL: 125 to 500 mg 3 to 4 times daily (Prod Info penicillin V potassium oral tablet, powder for solution, 2010)

13) PIPERACILLIN

a) SERIOUS INFECTIONS: 12 to 18 g/day IV (200 to 300 mg/kg/day) in divided doses every 4 to 6 hours (Prod Info PIPRACIL(R) injection, 2004)
b) URINARY TRACT INFECTIONS (COMPLICATED): 8 to 16 g/day IV (125 to 200 mg/ kg/day) in divided doses every 6 to 8 hours (Prod Info PIPRACIL(R) injection, 2004)
c) URINARY TRACT INFECTIONS (UNCOMPLICATED): 6 to 8 g/day IM or IV (100 to 125 mg/kg/day) in divided doses every 6 to 12 hours (Prod Info PIPRACIL(R) injection, 2004)

14) TICARCILLIN

a) GYNECOLOGIC INFECTIONS: 200 mg/kg/day IV every 6 hours and for severe infections, 300 mg/kg/day in divided doses every 4 hours by infusion given over 30 minutes (Prod Info TIMENTIN(R) IV injection, 2010).
b) For patients weighing less than 60 kg: Recommended dosage is 200 to 300 mg/kg/day, based on ticarcillin content, given in divided doses every 4 to 6 hours (Prod Info TIMENTIN(R) IV injection, 2010).
c) URINARY TRACT INFECTIONS: 3 g every 4 to 6 hours for average (60 kg) adults with systemic and uncomplicated UTIs (Prod Info TIMENTIN(R) IV injection, 2010)

7.2.2)

A) SPECIFIC SUBSTANCE

1) AMOXICILLIN

a) PEDIATRIC

1) USUAL DOSE: 3 months of age and younger: 30 mg/kg/day orally divided every 12 hours (Prod Info AMOXIL(R) oral capsules, tablets, chewable tablets, and powder for oral suspension, 2009).
2) USUAL DOSE Greater than 3 months of age: 25 to 45 mg/kg/day orally divided every 12 hours (maximum 500 mg/dose) or 20 to 40 mg/kg/day divided every 8 hours (maximum 250 mg/dose) (Prod Info AMOXIL(R) oral capsules, tablets, chewable tablets, and powder for oral suspension, 2009).
3) ACUTE OTITIS MEDIA: 2 months of age and older: 80 to 90 mg/kg/day orally divided every 12 hours for 5 to 7 days (6 years and older) or 10 days (children less than 6 years or severe illness) (Arguedas et al, 2005; American Academy of Pediatrics Subcommittee on Management of Acute Otitis Media, 2004; Piglansky et al, 2003; Dowell et al, 1999; Canafax et al, 1998).
4) COMMUNITY-ACQUIRED PNEUMONIA: S. pneumoniae (MIC less than or equal to 2 mcg/mL): 3 month of age and older: 90 mg/kg/day orally in 2 divided doses; total treatment duration of 10 days (Bradley et al, 2011). Maximum: 3 g/day.
5) COMMUNITY-ACQUIRED PNEUMONIA: Group A Streptococcus: 3 months of age and older: 50 to 75 mg/kg/day orally in 2 divided doses; total treatment duration of 10 days (Bradley et al, 2011). Maximum 3 g/day.
6) COMMUNITY-ACQUIRED PNEUMONIA: H. influenzae (beta-lactamase negative): 3 months of age and older: 75 to 100 mg/kg/day orally in 3 divided doses; total treatment duration of 10 days (Bradley et al, 2011). Maximum 3 g/day.
7) HELICOBACTER PYLORI INFECTION: 50 mg/kg/day orally divided every 12 hours (maximum 1 g/dose). Give in combination with clarithromycin 15 to 20 mg/kg/day orally divided every 12 hours (maximum 500 mg/dose) and omeprazole 1 mg/kg/day orally divided every 12 hours (maximum 20 mg/dose) for 7 to 14 days (Koletzko et al, 2011; Dehghani et al, 2009; Bourke et al, 2005; Francavilla et al, 2005; Gottrand et al, 2001; Gold et al, 2000).

a) Metronidazole 20 mg/kg/day orally divided every 12 hours (maximum 500 mg/dose) can be used in place of clarithromycin (Koletzko et al, 2011; Gold et al, 2000).

8) INFECTIVE ENDOCARDITIS, PROPHYLAXIS: (high-risk patients; dental, respiratory or infected skin/skin structure procedures): 50 mg/kg orally 30 to 60 minutes prior to procedure. Maximum 2 g/dose (Wilson et al, 2007a).
9) LYME DISEASE: 50 mg/kg/day orally in 3 divided doses (maximum 500 mg/dose) for 14 days (range, 14 to 21 days) for early localized or early disseminated Lyme disease associated with erythema migrans, or Lyme carditis to complete a course of therapy or to treat ambulatory patients, or seventh-cranial-nerve palsy with no central nervous system involvement or borrelial lymphocytoma; for 28 days for Lyme arthritis without neurological involvement; for 21 days for acrodermatitis chronica atrophicans (Tory et al, 2010; Wormser et al, 2006; Eppes & Childs, 2002).
10) PHARYNGITIS, TONSILLITIS: (extended-release tablet): 12 years of age and older, 775 mg orally once daily for 10 days (Prod Info MOXATAG(TM) oral extended-release tablets, 2008).
11) STREPTOCOCCAL PHARYNGITIS: 50 mg/kg orally once daily for 10 days; maximum 1 g daily (Gerber et al, 2009; Lennon et al, 2008; Clegg et al, 2006; Feder et al, 1999).

2) AMOXICILLIN/CLARITHROMYCIN/LANSOPRAZOLE

a) Safety and effectiveness have not been established in pediatric patients (Prod Info PREVPAC(TM) oral delayed-release capsules, oral capsules, oral tablets, 2014).

3) AMOXICILLIN/CLARITHROMYCIN/OMEPRAZOLE

a) Safety and effectiveness have not been established in pediatric patients (Prod Info Omeclamox-Pak(TM) oral kit, 2015).

4) AMPICILLIN

a) ORAL: USUAL DOSE: 50 to 100 mg/kg/day orally divided every 6 hours. Maximum 2 g/day (Prod Info ampicillin capsules, oral suspension, 2004).
b) PARENTERAL: USUAL DOSE: 100 to 200 mg/kg/day IV or IM divided every 6 hours (Committee on Infectious Diseases, American Academy of Pediatrics et al, 2009; Prod Info ampicillin IM, IV injection, 2009). Maximum 2 g/dose.
c) BACTERIAL MENINGITIS: 300 to 400 mg/kg/day IV divided every 6 hours. Maximum 3 g/dose (Kim, 2010; Committee on Infectious Diseases, American Academy of Pediatrics et al, 2009; Tunkel et al, 2004; Marks et al, 1986; None Listed, 1982). Suggested duration of therapy is 7 days for N. meningitidis and H. influenzae, 10 to 14 days for S. pneumoniae, 14 to 21 days for S. agalactiae, 21 days for gram negative bacilli, and at least 21 days for L. monocytogenes (Tunkel et al, 2004a).
d) COMMUNITY-ACQUIRED PNEUMONIA: S. pneumoniae (MIC less than or equal to 2 mcg/mL) and H. influenzae (beta-lactamase negative): 3 months and older, 150 to 200 mg/kg/day IV divided every 6 hours for 10 days (Bradley et al, 2011). Maximum 2 g/dose.
e) COMMUNITY-ACQUIRED PNEUMONIA: Group A Streptococcus: 3 months and older, 200 mg/kg/day IV divided every 6 hours for 10 days (Bradley et al, 2011). Maximum 2 g/dose.
f) INFECTIVE ENDOCARDITIS: Enterococcal Strains Susceptible to Penicillin, Gentamicin, and Vancomycin: 300 mg/kg/day IV divided every 4 to 6 hours (maximum dose 12 g/day) AND gentamicin sulfate 1 mg/kg IV/IM every 8 hours for 4 to 6 weeks (Baddour et al, 2005).
g) INFECTIVE ENDOCARDITIS: Enterococcal Strains Susceptible to Penicillin, Streptomycin, and Vancomycin, and Resistant To Gentamicin: 300 mg/kg/day IV divided every 4 to 6 hours (maximum dose 12 g/day) AND streptomycin 10 to 15 mg/kg IV/IM every 12 hours for 4 to 6 weeks (Baddour et al, 2005).
h) INFECTIVE ENDOCARDITIS: Enterococcus faecalis Strains Resistant to Penicillin, Aminoglycoside, and Vancomycin: 300 mg/kg/day IV divided every 4 to 6 hours (maximum dose 12 g/day), in combination with either imipenem/cilastatin 15 to 25 mg/kg IV every 6 hours (maximum 500 mg/dose) or ceftriaxone 50 mg/kg IV/IM every 12 hours (maximum 2 g/dose) for at least 8 weeks (Baddour et al, 2005).
i) INFECTIVE ENDOCARDITIS: Prophylaxis: 50 mg/kg IV or IM 30 to 60 minutes prior to dental procedure. Maximum 2 g/dose (Wilson et al, 2007).

5) DICLOXACILLIN

a) INFECTION DUE TO STAPHYLOCOCCUS AUREUS

1) Weight less than 40 kg: Mild to moderate infections: 12.5 mg/kg/day in equally divided doses every 6 hours. Severe infections: 25 mg/kg/day in equally divided doses every 6 hours; continue for at least 14 days and a minimum of 48 hours after resolution of symptoms and cultures are negative (Prod Info dicloxacillin sodium oral capsule, 2010).
2) Weight more than 40 kg: Mild to moderate infections: 125 mg/kg/day every 6 hours. Severe infections: 250 mg/kg/day every 6 hours; continue for at least 14 days and a minimum of 48 hours after resolution of symptoms and cultures are negative. Endocarditis and osteomyelitis treatment may require a longer term of therapy (Prod Info dicloxacillin sodium oral capsule, 2010).

b) GROUP A BETA-HEMOLYTIC STREPTOCOCCAL

1) Treat group A beta-hemolytic streptococci infections for a minimum of 10 days to help prevent the occurrence of acute rheumatic fever or acute glomerulonephritis (Prod Info dicloxacillin sodium oral capsule, 2010).

6) NAFCILLIN

a) Bacterial Meningitis (methicillin-susceptible Staphylococcus aureus): 29 days and older: 200 mg/kg/day IV divided every 6 hours (Tunkel et al, 2004a). Maximum 2 g/dose.
b) Community-Acquired Pneumonia: 3 months of age and older: 150 to 200 mg/kg/day IV divided every 6 to 8 hours for 10 days (Bradley et al, 2011). Maximum 2 g/dose.
c) Infective Endocarditis (oxacillin-susceptible Staphylococcus strains): Native valve: 29 days of age and older: 200 mg/kg/day IV (maximum 12 g/day) in 4 to 6 equally divided doses for 6 weeks WITH or WITHOUT gentamicin sulfate 1 mg/kg IV/IM every 8 hr for 3 to 5 days (Baddour et al, 2005a). Maximum 2 g/dose.
d) Infective Endocarditis (oxacillin-susceptible Staphylococcus strains): Prosthetic valve: 29 days of age and older: 200 mg/kg/day IV (maximum 12 g/day) in 4 to 6 equally divided doses AND rifampin 20 mg/kg/day IV or orally (maximum 900 mg/day) in 3 equally divided doses for a minimum of 6 weeks AND gentamicin sulfate 1 mg/kg IV/IM every 8 hours for 2 weeks (Baddour et al, 2005a). Maximum 2 g/dose.
e) Serious Staphylococcal Infections (due to penicillinase-producing staphylococci): 29 days of age and older, 150 to 200 mg/kg/day IV or IM divided every 4 to 6 hours (Martinez-Aguilar et al, 2004; Johnson et al, 1988; Fan-Havard & Nahata, 1987; Armstrong & Rush, 1983; Norden et al, 1983; Kaplan et al, 1982; Yogev et al, 1981; Prober & Yeager, 1979; Feldman et al, 1978). Maximum 2 g/dose.

7) PENICILLIN G BENZATHINE (IM)

a) Rheumatic Fever, Recurrent; Prophylaxis: 27 kg or less: 600,000 units IM every 4 weeks; high-risk patients, given every 3 weeks (Gerber et al, 2009)
b) Rheumatic Fever, Recurrent; Prophylaxis: Greater than 27 kg: 1,200,000 units IM every 4 weeks; high-risk patients, given every 3 weeks (Gerber et al, 2009)
c) Streptococcal (group A) Upper Respiratory Infection (pharyngitis): 27 kg or less: 600,000 units IM as a single dose (Gerber et al, 2009)
d) Streptococcal (group A) Upper Respiratory Infection (pharyngitis): Greater than 27 kg: 900,000 units IM as a single dose (Gerber et al, 2009)
e) Syphilis: Primary, Secondary, and Early Latent: 30 days and older: 50,000 units/kg IM as a single dose. Maximum 2.4 million units/dose (Centers for Disease Control and Prevention, 2010)
f) Syphilis: Late Latent or Unknown Duration: 30 days and older: 50,000 units/kg IM (maximum 2.4 million units/dose) administered as 3 doses at 1-week intervals (total 150,000 units/kg up to a maximum dose of 7.2 million units) (Centers for Disease Control and Prevention, 2010).
g) Syphilis: Congenital: No clinical manifestations of disease, CSF normal, and CSF VDRL is negative: 30 days and older: 50,000 units/kg IM (maximum 2.4 million units/dose) weekly for up to 3 doses (Centers for Disease Control and Prevention, 2010).
h) Syphilis: Neurologic involvement: 30 days and older: 50,000 units/kg IM (maximum 2.4 million units/dose) for a single dose after 10-day course of IV aqueous penicillin G (Centers for Disease Control and Prevention, 2010).

8) PENICILLIN G BENZATHINE/PENICILLIN G PROCAINE

a) BICILLIN(R) C-R

1) PNEUMOCOCCAL INFECTION (EXCLUDING PNEUMOCOCCAL MENINGITIS): The recommended dose is 600,000 units IM repeated every 2 or 3 days until temperature is normal for 48 hours (Prod Info Bicillin(R) C-R intramuscular injection suspension, 2015).
2) STREPTOCOCCAL INFECTION AND WEIGHING GREATER THAN 27 KG: The recommended dose is 2,400,000 units administered via multiple IM sites (Prod Info Bicillin(R) C-R intramuscular injection suspension, 2015)
3) STREPTOCOCCAL INFECTION AND WEIGHING 14 TO 27 KG: The recommended dose is 900,000 to 1,200,000 units administered via multiple IM sites (Prod Info Bicillin(R) C-R intramuscular injection suspension, 2015)
4) STREPTOCOCCAL INFECTION AND WEIGHING LESS THAN 14 KG: The recommended dose is 600,000 units administered via multiple IM sites (Prod Info Bicillin(R) C-R intramuscular injection suspension, 2015)

b) BICILLIN(R) C-R 900/300

9) PENICILLIN G PROCAINE (IM)

a) Usual Dose: Less than 27 kg: 300,000 units IM daily (Prod Info penicillin G procaine suspension for IM injection, 2006).
b) 27 kg and greater: 600,000 to 1,000,000 units IM daily (Prod Info penicillin G procaine suspension for IM injection, 2006).

10) PENICILLIN V

a) COMMUNITY ACQUIRED PNEUMONIA MILD TO MODERATE

1) Group A Streptococcus: 3 months and older: 50 to 75 mg/kg/day orally in 3 or 4 divided doses; total treatment duration of 10 days (Bradley et al, 2011). Maximum dose 1500 mg/day.

b) PNEUMOCOCCAL INFECTION PROPHYLAXIS FUNCTIONAL OR ANATOMIC ASPLENIA

1) Less than 5 years of age: 125 mg orally twice daily (Price et al, 2007; Castagnola & Fioredda, 2003; Gaston et al, 1986).
2) 5 years and older: 125 mg orally twice daily (Price et al, 2007; Castagnola & Fioredda, 2003; Gaston et al, 1986).

c) RHEUMATIC FEVER SECONDARY PREVENTION

1) 2 years and older: 250 mg orally twice daily (Gerber et al, 2009).
2) Duration of therapy depends on risk factors (multiple rheumatic fever attacks, increased exposure to group A streptococcal infection) as well as residual heart damage:

d) STREPTOCOCCAL PHARYNGITIS

1) FLAT DOSING

a) 27 kg or less: 250 mg orally 2 or 3 times daily for 10 days (Gerber et al, 2009)
b) Greater than 27 kg: 500 mg 2 or 3 times daily for 10 days (Gerber et al, 2009).

2) WEIGHT BASED DOSING

a) 2 years and older: 500 mg 2 or 3 times daily for 10 days (Gerber et al, 2009). Maximum dose 1500 mg/day.

11) TICARCILLIN INTRAVENOUS

a) USUAL DOSE

1) Mild-to-Moderate Infection: 30 days of age and older: 200 mg/kg/day (based on ticarcillin content) IV divided every 6 hours (Prod Info TIMENTIN(R) IV injection, 2010). Maximum 3.1 g/dose.
2) Mild-to-Moderate Infection: Greater than 60 g: 3.1 g of Timentin(R) (3 g of ticarcillin and 100 mg of clavulanic acid) administered every 6 hours (Prod Info TIMENTIN(R) IV injection, 2010).
3) Severe Infection: 30 days of age and older: 300 mg/kg/day (based on ticarcillin content) IV divided every 4 to 6 hours. Maximum 3.1 g/dose (Prod Info TIMENTIN(R) IV injection, 2010; Blumer, 1998; Dougherty et al, 1995; Sirinek & Levine, 1991; Pokorny et al, 1991; Jacobs & Elser, 1989; Gooch et al, 1985).
4) Severe infection: Greater than 60 g: 3.1 g of Timentin(R) (3 g of ticarcillin and 100 mg of clavulanic acid) every 4 hours (Prod Info TIMENTIN(R) IV injection, 2010).
5) Based on pharmacokinetic/pharmacodynamic assessments of ticarcillin/clavulanate in infants and children, it has been suggested that a dose of 75 to 80 mg/kg (ticarcillin component) every 8 hours would be appropriate for treating susceptible infections in infants and children (Reed, 1998; Reed et al, 1995).
6) Renal impairment: There are no data available for pediatric patients with renal impairment; however, the following dose adjustments are based on recommendations for adults with renal impairment (Prod Info TIMENTIN(R) IV injection, 2010):
7) Give usual initial dose (eg, 50 mg/kg ticarcillin component) then adjust appropriately:
8) CrCl 30 to 60 mL/min: Decrease usual dose by 33% and give at usual intervals.
9) CrCl 10 to 30 mL/min: Decrease usual dose by 33% and give every 8 hours.
10) CrCl less than 10 mL/min: Decrease usual dose by 33% and give every 12 hours.
11) CrCl less than 10 mL/min and hepatic impairment: Decrease usual dose by 33% and give every 24 hours.
12) Hemodialysis: Decrease usual dose by 33% and give every 12 hours; supplement with a usual dose after hemodialysis.
13) Peritoneal dialysis: Give usual dose every 12 hours.
14) Continuous venovenous hemofiltration (CVVH): Based on data from 3 pediatric patients, the increased clearance of clavulanic acid by CVVH may result in the loss of beta-lactamase inhibition (Lindsay et al, 1996)

Maximum Tolerated Exposure

1) AMOXICILLIN

a) In a prospective study of 51 cases of ingestion of amoxicillin 250 mg/kg or less in children younger than 6 years, 80% remained completely asymptomatic without gastric decontamination. Symptoms that did develop within 72 hours of ingestion were limited to 1 to 2 episodes of loose stools (7 of 51 patients), stomachache, and low-grade fever (1 of 51 patients). However, the individual means, medians, and dose distributions for each of these agents were not available (Swanson-Biearman et al, 1988).
b) CASE REPORT: A 4-year-old boy developed reversible acute tubulointerstitial nephritis following an inadvertent overdose of 240 mg/kg of amoxicillin. Difficulty passing urine and gross hematuria occurred within 2 hours of overdose; the patient recovered completely with supportive care (Schellie & Groshong, 1999).
c) CASE REPORT: Crystalluria occurred in a 2-year-old boy 1.5 hours after he ingested 6.375 g (580 mg/kg) of amoxicillin suspension. The patient recovered following IV saline administration (Selzer & Roberts, 1997).
d) CASE REPORTS: Acute renal failure was also reported in 2 children (ages 2.5 and 7 years) after inadvertently ingesting 7.5 to 12 g and 6 g of amoxicillin, respectively. Early symptoms included vomiting, abdominal pain and hematuria. The youngest child became lethargic about 16 hours after exposure. Both recovered completely with supportive care (Jones et al, 1993).
e) CASE REPORT: A 3-year-old boy, with no history of renal disease, developed nausea, vomiting, and acute renal failure following ingestion of a single dose of amoxicillin 574 mg/kg (Geller et al, 1986).

2) AMPICILLIN

a) Symptoms developed in 2 of 3 patients ingesting ampicillin (ie, loose stools and a self-limited rash) at less than 250 mg/kg. However, the individual mean, median, and dose distribution for this agent was not available (Swanson-Biearman et al, 1988).

3) PENICILLIN

a) INTRAVENOUS: Agitation, confusion, hallucinations, stupor, coma multifocal myoclonus, seizures and encephalopathy may occur following massive doses of IV penicillins (40 to 100 million units/day); patients with renal impairment may be at increased risk (Prod Info penicillin G sodium IV, IM injection, 2009).
b) Patients with normal renal function can frequently tolerate very large doses of penicillins without experiencing toxicity, although anaphylaxis and intestinal distress can occur following very low doses (including intradermal skin testing).
c) Penicillin in single doses of 10 million units (6 g) or more intravenously may result in CNS irritation with seizures and coma (Weinstein et al, 1964; Lerner et al, 1967; Conway et al, 1968).

Serum Plasma Blood Concentrations

7.5.2)

A) TOXIC CONCENTRATION LEVELS

1) PENICILLIN

a) SERUM: Weinstein et al (1964) reported a patient who developed seizures with serum penicillin concentrations of 737 units (433 mcg/mL, 2 hours after intravenous administration of 10 million units (6 g).
b) CSF penicillin levels greater than 8 units (5 mcg/mL may result in seizure (Lerner et al, 1967).

Pharmacology Toxicology

Pharmacologic Mechanism

1) All penicillins contain 6-aminopenicillanic acid (6-APA), which is composed of a thiazolidine ring and a beta-lactam ring as a part of their chemical structure.
2) Addition of various chains by acylation of the 6-amino group of 6-APA yields semisynthetic penicillins (eg, amoxicillin, ampicillin, carbenicillin, cloxacillin, dicloxacillin, hetacillin, methicillin, nafcillin, oxacillin, and phenethicillin).
3) These drugs differ in antibacterial spectra, resistance to inactivation by gastric acid, absorption, resistance to penicillinase, and protein binding.

1) The antibacterial action of the penicillins resides in their ability to inhibit metabolic functions vital to synthesis of the bacterial cell wall.
2) In general, the penicillins are active against gram positive cocci and bacilli and some gram negative cocci.
3) In addition, the broad spectrum penicillins, eg, amoxicillin, ampicillin, carbenicillin, and hetacillin, are active against some additional gram negative bacilli.

Toxicologic Mechanism

Physicochemical

Animal Toxicology

Clinical Effects

11.1.13)

A) OTHER

1) Reports of hypersensitivity to penicillin or other antibiotics are not common in animals.

Treatment

11.2.1)

A) GENERAL TREATMENT

1) Begin treatment immediately.
2) Keep animal warm and do not handle unnecessarily.
3) Sample vomitus, blood, urine, and feces for analysis.
4) Remove the patient and other animals from the source of contamination.
5) Treatment should always be done on the advice and with the consultation of a veterinarian.

a) Additional information regarding treatment of poisoned animals may be obtained from a Board Certified (ABVT) Veterinary Toxicologist (check with nearest veterinary school or veterinary diagnostic laboratory) or the National Animal Poison Control Center.

6) ANIMAL POISON CONTROL CENTERS

a) ASPCA Animal Poison Control Center, An Allied Agency of the University of Illinois, 1717 S. Philo Rd, Suite 36, Urbana, IL 61802, website www.aspca.org/apcc
b) It is an emergency telephone service which provides toxicology information to veterinarians, animal owners, universities, extension personnel and poison center staff for a fee. A veterinary toxicologist is available for consultation.
c) The following 24-hour phone number is available: (888) 426-4435. A fee may apply. Please inquire with the poison center. The agency will make follow-up calls as needed in critical cases at no extra charge.

11.2.2)

A) GENERAL

1) MAINTAIN VITAL FUNCTIONS: Secure airway, supply oxygen, and begin supportive fluid therapy if necessary.

11.2.4)

A) GASTRIC DECONTAMINATION

1) DOGS/CATS

a) Discontinue administration of the penicillin.
b) OCULAR: Rinse eyes with copious amounts of tepid water for 15 minutes. If irritation, pain, or photophobia persists, see your veterinarian.
c) INHALATION: Move patient to fresh air. Monitor patient for respiratory distress. Emergency airway support and supplemental oxygen with assisted ventilation may be needed.

1) If a cough or difficulty in breathing develops, evaluate for respiratory tract irritation or bronchitis.

d) DERMAL: In case of dermatologic exposure, bathe in mild detergent (animal shampoo or Ivory liquid). Wear gloves to avoid human exposure. Clip hair as necessary to facilitate removal.
e) EMESIS AND LAVAGE: If within 2 hours of exposure, induce emesis with 1 to 2 mL/kg syrup of ipecac orally.

1) Dogs may vomit more readily with 1 tablet (6 mg) apomorphine diluted in 3 to 5 mL water and instilled into the conjunctival sac or orally.
2) Dogs may also be given apomorphine intravenously at 40 mcg/kg. Do not use an emetic if the animal is hypoxic. In the absence of a gag reflex or if vomiting cannot be induced, place a cuffed endotracheal tube and begin gastric lavage.
3) Pass large bore stomach tube and instill 5 to 10 mL/kg water or lavage solution, then aspirate. Repeat 10 times.

f) ACTIVATED CHARCOAL: Administer activated charcoal 2 g/kg orally or via stomach tube. Avoid aspiration by proper restraint, careful technique, and, if necessary, tracheal intubation.
g) CATHARTIC: Administer a dose of a saline cathartic such as magnesium or sodium sulfate (sodium sulfate dose is 1 g/kg). If access to these agents is limited, give 5 to 15 mL magnesium oxide (Milk of Magnesia) orally for dilution.

11.2.5)

A) DOGS/CATS

1) MAINTAIN VITAL FUNCTIONS as necessary.
2) ANAPHYLAXIS

a) AIRWAY: Maintain a patent airway via endotracheal tube or tracheostomy.
b) EPINEPHRINE: For severe reactions.

1) DOGS: 0.5 to 1 mL of 1:10,000 (DILUTE) solution intravenously or subcutaneously.
2) CATS : 0.5 mL of 1:10,000 (DILUTE) solution intravenously or intramuscularly.
3) Be sure to dilute epinephrine from the bottle (1:1000) 1 part to 9 parts saline to obtain the correct concentration (1:10,000). If indicated, dose may be repeated in 20 minutes.

c) FLUID THERAPY: If necessary, begin fluid therapy at maintenance doses (66 mL solution/kg/day intravenously) or, in hypotensive patients, at high doses (up to shock dose 60 mL/kg/hr).

1) Monitor for urine production and pulmonary edema.

d) ANTIHISTAMINES/STEROIDS: Administer doxylamine succinate (1 to 2.2 mg/kg subcutaneously or intramuscularly every 8 to 12 hours), dexamethasone sodium phosphate (1 to 5 mg/kg intravenously every 12 to 24 hours), or prednisolone (1 to 5 mg/kg intravenously every 1 to 6 hours).

Continuing Care

11.4.1)

11.4.1.2) DECONTAMINATION/TREATMENT

A) GENERAL TREATMENT

6) ANIMAL POISON CONTROL CENTERS

11.4.2)

11.4.2.2) GASTRIC DECONTAMINATION

A) GASTRIC DECONTAMINATION

1) DOGS/CATS

1) If a cough or difficulty in breathing develops, evaluate for respiratory tract irritation or bronchitis.

References

General Bibliography

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FeedBack

PENICILLIN

Classification | Detailed evidence-based information

Therapeutic Toxic Class

Specific Substances

Available Forms Sources

Life Support

Clinical Effects

Laboratory Monitoring

Treatment Overview

Range Of Toxicity

Summary Of Exposure

Vital Signs

Heent

Cardiovascular

Respiratory

Neurologic

Gastrointestinal

Hepatic

Genitourinary

Hematologic

Dermatologic

Immunologic

Reproductive

Monitoring Parameters Levels

Life Support

Patient Disposition

Monitoring

Oral Exposure

Enhanced Elimination

Case Reports

Summary

Therapeutic Dose

Maximum Tolerated Exposure

Serum Plasma Blood Concentrations

Pharmacologic Mechanism

Toxicologic Mechanism

Clinical Effects

Treatment

Continuing Care

General Bibliography