Dosing & Uses
Dosing Form & Strengths
penicillin G benzathine/penicillin G procaine
injectable suspension
- 600,000units/600,000units/2mL (ie, 1.2 million units/2mL)
- 900,000units/300,000units/2mL (ie, 1.2 million units/2mL)
Streptococcal Group A Infections
Indicated for moderately severe-to-severe infections of upper-respiratory tract, scarlet fever, erysipelas, and skin and soft-tissue infections caused by streptococcal Group A
2.4 million units IM x1; divided dosage administration into multiple site
Alternatively, administer 1.2 million units IM on day 1, then repeat dose on day 3
Pneumococcal Infections
NOT for pneumococcal meningitis
1.2 million units IM; repeat q2-3 days until temperature is normal for 48 hr; other penicillin forms (ie, IV) necessary for severe infection
Renal Impairment
CrCl 10-50 mL/min: Decrease dose by 25%
CrCl <10 mL/min: Decrease dose by 50-70%
Hemodialysis: Removed by hemodialysis; administer after dialysis
Dosing Form & Strengths
penicillin G benzathine/penicillin G procaine
injectable suspension
- 600,000units/600,000units/2mL (ie, 1.2 million units/2mL)
- 900,000units/300,000units/2mL (ie, 1.2 million units/2mL)
Streptococcal Group A Infections
Indicated for moderately severe-to-severe infections of upper-respiratory tract, scarlet fever, erysipelas, and skin and soft-tissue infections caused by streptococcal Group A
Bicillin C-R
- <14 kg: 600,000 units IM x1
- 14-27 kg: 900,000-1,200,000 units IM x1
- 27 kg or more: As adults; 2.4 million units IM x1; divided dosage administration into multiple site; alternatively, administer 1.2 million units IM on day 1, then repeat dose on day 3
Bicillin C-R 900/300
- 900 units/300 units IM x1
Pneumococcal Infections
NOT for pneumococcal meningitis
Bicillin C-R: 600,000 units IM; repeat q2-3 days until temperature is normal for 48 hr; other penicillin forms (ie, IV) necessary for severe infection
Bicillin C-R 900/300: 900 units/300 units IM; repeat q2-3 days until temperature is normal for 48 hr; other penicillin forms (ie, IV) necessary for severe infection
Renal Impairment
Not defined in children; see adult recommendations
Interactions
Interaction Checker
No Results

Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor

Contraindicated (0)
Serious - Use Alternative (8)
- baricitinib
penicillin G benzathine will increase the level or effect of baricitinib by decreasing elimination. Avoid or Use Alternate Drug. Coadministration of baricitinib with strong organic anion transporter 3 (OAT3) inhibitors is not recommended.
- cholera vaccine
penicillin G benzathine, cholera vaccine. pharmacodynamic antagonism. Avoid or Use Alternate Drug. Avoid coadministration of cholera vaccine with systemic antibiotics since these agents may be active against the vaccine strain. Do not administer cholera vaccine to patients who have received oral or parenteral antibiotics within 14 days prior to vaccination.
penicillin G procaine, cholera vaccine. pharmacodynamic antagonism. Avoid or Use Alternate Drug. Avoid coadministration of cholera vaccine with systemic antibiotics since these agents may be active against the vaccine strain. Do not administer cholera vaccine to patients who have received oral or parenteral antibiotics within 14 days prior to vaccination. - leniolisib
leniolisib will increase the level or effect of penicillin G benzathine by Other (see comment). Avoid or Use Alternate Drug. Leniolisib, an OATP1B1 and OATP1B3 inhibitor, may increase systemic exposure of these substrates
- microbiota oral
penicillin G procaine decreases effects of microbiota oral by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Microbiota oral contains bacterial spores. Antibacterial agents may decrease efficacy if coadministered. Complete antibiotic regimens 2-4 days before initiating microbiota oral. .
- microbiota oral
penicillin G benzathine decreases effects of microbiota oral by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Microbiota oral contains bacterial spores. Antibacterial agents may decrease efficacy if coadministered. Complete antibiotic regimens 2-4 days before initiating microbiota oral. .
- omadacycline
omadacycline decreases effects of penicillin G procaine by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Tetracyclines may interfere with the bactericidal action of penicillins. Monitor for decreased therapeutic effects of penicillins if concomitantly used with a tetracycline.
omadacycline decreases effects of penicillin G benzathine by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Tetracyclines may interfere with the bactericidal action of penicillins. Monitor for decreased therapeutic effects of penicillins if concomitantly used with a tetracycline. - sarecycline
sarecycline decreases effects of penicillin G benzathine by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Tetracyclines may interfere with the bactericidal action of penicillins. Monitor for decreased therapeutic effects of penicillins if concomitantly used with a tetracycline.
sarecycline decreases effects of penicillin G procaine by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Tetracyclines may interfere with the bactericidal action of penicillins. Monitor for decreased therapeutic effects of penicillins if concomitantly used with a tetracycline. - trofinetide
trofinetide will increase the level or effect of penicillin G benzathine by Other (see comment). Avoid or Use Alternate Drug. Trofinetide (an OATP131 and OATP13B inhibitor) may increase plasma levels of OATP131 or OATP13B substrates. Avoid coadministration with sensitive substrates.
Monitor Closely (5)
- amifampridine
penicillin G benzathine increases toxicity of amifampridine by Other (see comment). Modify Therapy/Monitor Closely. Comment: Amifampridine can cause seizures. Coadministration with drugs that lower seizure threshold may increase this risk.
penicillin G procaine increases toxicity of amifampridine by Other (see comment). Modify Therapy/Monitor Closely. Comment: Amifampridine can cause seizures. Coadministration with drugs that lower seizure threshold may increase this risk. - apalutamide
apalutamide will decrease the level or effect of penicillin G benzathine by increasing elimination. Use Caution/Monitor. Apalutamide weakly induces OATP1B1 and may decrease systemic exposure of drugs that are OATP1B1 substrates.
- dienogest/estradiol valerate
penicillin G procaine will decrease the level or effect of dienogest/estradiol valerate by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor. An alternate or additional form of birth control may be advisable during concomitant use.
- dienogest/estradiol valerate
penicillin G benzathine will decrease the level or effect of dienogest/estradiol valerate by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor. An alternate or additional form of birth control may be advisable during concomitant use.
- sodium picosulfate/magnesium oxide/anhydrous citric acid
penicillin G procaine decreases effects of sodium picosulfate/magnesium oxide/anhydrous citric acid by altering metabolism. Use Caution/Monitor. Coadministration with antibiotics decreases efficacy by altering colonic bacterial flora needed to convert sodium picosulfate to active drug.
penicillin G benzathine decreases effects of sodium picosulfate/magnesium oxide/anhydrous citric acid by altering metabolism. Use Caution/Monitor. Coadministration with antibiotics decreases efficacy by altering colonic bacterial flora needed to convert sodium picosulfate to active drug.
Minor (0)
Adverse Effects
Frequency Not Defined
Skin rashes including maculopapular eruptions and exfoliative dermatitis
Urticaria
Serum-sicknesslike reactions (eg, chills, fever, edema, arthralgia, prostration)
Jarisch-Herxheimer reaction reported when treating syphilis
Pseudomembranous colitis
Warnings
Black Box Warnings
Not for IV use
Do not inject IV or admix with other IV solutions
Reports of inadvertent IV administration associated with cardiorespiratory arrest and death
Prior to administration, carefully read the warnings, adverse reactions, and dosage and administration sections of the labeling
Contraindications
Hypersensitivity; serious and occasionally fatal reactions have been reported
Cautions
For deep IM administration only; do not administer IV, SC, or IT
Severe cutaneous adverse reactions (SCAR), such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP) reported; discontinue therapy when SCAR suspected; consider an alternative treatment
Procaine reactions: Immediate toxic reactions to procaine reported, particularly when a large single dose is administered (4.8 million units); reaction manifested by mental disturbances including anxiety, confusion, agitation, depression, weakness, seizures, hallucinations, combativeness, and fear
Avoid use in neonates; increased risk for sterile abscess development and procaine toxicity
Severe pneumonia, empyema, bacteremia, pericarditis, meningitis, peritonitis, and arthritis of pneumococcal etiology are better treated with penicillin G sodium or potassium during the acute stage
When high, sustained serum levels are required, penicillin G sodium or potassium, either IM or IV, should be used
NOT indicated for treatment of venereal diseases, including syphilis, gonorrhea, yaws, bejel, and pinta
Only prescribe combination of penicillin G benzathine and penicillin G procaine for the approved indications
Prescribing in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to patient and increases the risk of a development of drug-resistant bacteria
For deep intramuscular injection only; there have been reports of inadvertent intravenous administration of penicillin G benzathine which has been associated with cardiorespiratory arrest and death; therefore, do not inject intravenously or admix with other intravenous solutions
Administer intramuscularly only in the upper, outer quadrant of the buttock (dorsogluteal) or ventrogluteal site; quadriceps femoris fibrosis and atrophy reported following repeated intramuscular injections of penicillin preparations into anterolateral thigh; therefore, administration in anterolateral thigh not recommended
In prolonged therapy with penicillin, and particularly with high-dosage schedules, periodic evaluation of renal and hematopoietic systems is recommended
The use of antibiotics may result in overgrowth of nonsusceptible organisms; constant observation of patient is essential; if new infections due to bacteria or fungi appear during therapy, the drug should be discontinued and appropriate measures taken.
Anaphylaxis or allergic reactions
- Serious and rare fatal hypersensitivity, anaphylactic, reactions reported in patients on penicillin therapy; reactions are more likely to occur in individuals with history of penicillin hypersensitivity and/or history of sensitivity to multiple allergens
- Individuals with history of penicillin hypersensitivity who experienced severe reactions when treated with cephalosporins reported
- Make careful inquiry regarding previous hypersensitivity reactions to penicillin, cephalosporins, or other allergens prior to initiating therapy with this penicillin combination
- If allergic reaction occurs, discontinue administration and institute appropriate therapy
- Serious anaphylactic reactions require immediate emergency treatment with epinephrine, oxygen, intravenous steroids, and airway management, including intubation as indicated
- Penicillin should be used with caution in individuals with histories of significant allergies and/or asthma
- A small percentage of patients are sensitive to procaine; if there is a history of sensitivity, make the usual test: inject intradermally 0.1 mL of a 1 to 2 percent procaine solution; development of an erythema, wheal, flare, or eruption indicates procaine sensitivity; sensitivity should be treated by the usual methods, including barbiturates, and procaine penicillin preparations should not be used; antihistaminics appear beneficial in treatment of procaine reactions
- Whenever allergic reactions occur, penicillin should be withdrawn unless, in the opinion of the physician, the condition being treated is life-threatening and amenable only to penicillin therapy
Clostridium difficile-associated diarrhea
- Clostridium difficile associated with diarrhea (CDAD) reported; may range in severity from mild diarrhea to fatal colitis; treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile
- C. difficile produces toxins A and B which contribute to development of CDAD; hyper toxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy
- CDAD must be considered in all patients who present with diarrhea following antibiotic use; careful medical history necessary since CDAD has been reported to occur over two months after administration of antibacterial agents
- If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued; appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated
Injection into or near a nerve
- Inadvertent intravascular administration, including inadvertent direct intra-arterial injection or injection immediately adjacent to arteries, has resulted in severe neurovascular damage, including transverse myelitis with permanent paralysis, gangrene requiring amputation of digits and more proximal portions of extremities, and necrosis and sloughing at and surrounding the injection site
- Such severe effects have been reported following injections into buttock, thigh, and deltoid areas; other serious complications of suspected intravascular administration which have been reported include immediate pallor, mottling, or cyanosis of extremity both distal and proximal to injection site, followed by bleb formation; severe edema requiring anterior and/or posterior compartment fasciotomy in the lower extremity
- The above-described severe effects and complications have most often occurred in infants and small children; prompt consultation with an appropriate specialist is indicated if any evidence of compromise of blood supply occurs at, proximal to, or distal to site of injection
Methemoglobinemia
- Use of local anesthetics may cause methemoglobinemia, a serious condition that must be treated promptly; patients with glucose-6-phosphate dehydrogenase deficiency, congenital or idiopathic methemoglobinemia, cardiac or pulmonary compromise, infants under 6 months of age, and concurrent exposure to oxidizing agents or their metabolites are more susceptible to developing clinical manifestations of the condition
- Patients who are administered local anesthetics are at increased risk of developing methemoglobinemia when concurrently exposed to the following drugs, nitroglycerin, nitroprusside, nitric oxide, nitrous oxide, cyclophosphamide, flutamide, hydroxyurea, ifosfamide, rasburicase, dapsone, nitrofurantoin, paraaminosalicylic acid, sulfonamides, chloroquine, primaquine, phenobarbital, sodium valproate, acetaminophen, metoclopramide, quinine, sulfasalazine
- Advise patients or caregivers to seek immediate medical attention if patient experiences the following signs or symptoms: pale, gray, or blue-colored skin (cyanosis); headache; rapid heart rate; shortness of breath; lightheadedness; or fatigue; discontinue drug and any other oxidizing agents; depending on severity of signs and symptoms, patients may respond to supportive care, including oxygen therapy and hydration; a more severe clinical presentation may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen
Pregnancy & Lactation
Pregnancy
Reproduction studies performed in the mouse, rat, and rabbit have revealed no evidence of impaired fertility or harm to fetus due to penicillin G
Human experience with penicillins during pregnancy has not shown any positive evidence of adverse effects on the fetus; there are, however, no adequate and well-controlled studies in pregnant women showing conclusively that harmful effects of these drugs on the fetus can be excluded
Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed
Lactation
Soluble penicillin G is excreted in breast milk; exercise caution when penicillin G benzathine and penicillin G procaine are administered to a nursing woman
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Half-Life: 20-30 minutes after hydrolysis to penicillin G
Absorption: IM, slow
Peak Plasma Time: 3 hr
Peak Plasma Concentration: 1-1.3 units/mL
Protein Bound: 60%
Metabolism: ~30% in liver
Excretion: urine (60-90%)
Mechanism of Action
Interferes with cell wall mucopeptide synthesis during active multiplication, resulting in bactericidal activity against susceptible microorganisms
Administration
IM Administration
Do not inject near artery or nerve (may result in permanent neurologic damage)
Neonates, infants, small children: Midlateral aspect of thigh preferable
Older children and adults: Deep IM injection in upper outer quadrant of buttock
Because of high concentration of suspended matter, needle may be blocked if injection is not made at slow, steady rate
Storage
Store refrigerated at 2-8 degrees C (36-46 degrees F)
Do not freeze
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