Penicillin G

The dosage of Penicillin G Potassium is highly individualized based on the type and severity of the infection, as well as the patient's renal function. Doses are typically measured in 'units' rather than milligrams.

• Serious Infections (e.g., Bacteremia, Pneumonia): Healthcare providers typically prescribe 5 million to 24 million units per day, divided into doses every 4 to 6 hours or given as a continuous IV infusion.
• Neurosyphilis: The standard recommendation is often 18 million to 24 million units per day, administered as 3 million to 4 million units IV every 4 hours for 10 to 14 days.
• Anthrax (Systemic): Doses may reach up to 24 million units per day, divided every 4 hours.
• Actinomycosis: 10 million to 20 million units per day for 2 to 6 weeks, followed by oral penicillin therapy.

For children and infants, dosing is calculated based on body weight.

• Neonates (under 28 days): The dosage is usually 50,000 to 100,000 units per kg per day, divided into two or three doses. In cases of severe infection like neonatal meningitis, the dose may be increased to 150,000 to 200,000 units per kg per day.
• Infants and Children: For serious infections, the typical range is 100,000 to 250,000 units per kg per day, divided into doses every 4 to 6 hours. The maximum pediatric dose generally does not exceed the maximum adult dose of 24 million units per day.

Renal Impairment

Because Penicillin G is primarily excreted by the kidneys, dosage adjustments are mandatory for patients with reduced renal function to prevent drug accumulation and toxicity (specifically neurotoxicity). If the Creatinine Clearance (CrCl) is less than 10 mL/min, healthcare providers may reduce the dose by 50% to 75% or extend the dosing interval to every 8 to 12 hours. Patients on hemodialysis may require a supplemental dose following the procedure, as the drug is dialyzable.

Hepatic Impairment

Generally, no dosage adjustment is required for patients with isolated liver disease, as the liver plays a minor role in the elimination of Penicillin G. However, if both renal and hepatic impairment are present, even more conservative dosing is necessary.

Elderly Patients

Older adults often have a natural decline in glomerular filtration rate (GFR). Healthcare providers will typically monitor kidney function closely and may start at the lower end of the dosing range to avoid complications like hyperkalemia (high potassium) or seizures.

Penicillin G Potassium is administered exclusively by healthcare professionals in a clinical setting (hospital or infusion center).

• Intravenous (IV): This is the most common route for severe infections. The drug is diluted in a compatible fluid (like Normal Saline or D5W) and infused over 30 to 60 minutes.
• Intramuscular (IM): If IV access is unavailable, the drug can be injected into a large muscle mass. However, this is often painful, and the volume of the dose may be limited.
• Storage: Before reconstitution, the powder should be stored at room temperature. Once reconstituted, the solution must be refrigerated and used within a specific timeframe (usually 24 hours to 7 days, depending on the manufacturer and diluent).

In a hospital setting, doses are scheduled strictly to maintain constant blood levels. If you are receiving home infusion and miss a dose, contact your nursing service or healthcare provider immediately. Do not double the next dose to catch up, as this increases the risk of potassium toxicity and seizures.

An overdose of Penicillin G Potassium can lead to neuromuscular hyperexcitability and convulsions (seizures). Furthermore, because this formulation contains potassium (approximately 1.7 mEq per 1 million units), a massive overdose can cause hyperkalemia. Symptoms of hyperkalemia include muscle weakness, fatigue, and dangerous heart rhythm disturbances. Emergency measures include discontinuing the infusion, administering anticonvulsants if seizures occur, and treating hyperkalemia with calcium gluconate, insulin/glucose, or dialysis if necessary.

> Important: Follow your healthcare provider's dosing instructions. Do not adjust your dose without medical guidance. Ensure you complete the full course of treatment even if symptoms improve early.

While Penicillin G is generally well-tolerated in patients without allergies, certain side effects occur frequently due to the nature of the administration and the drug's chemistry:

• Injection Site Reactions: Pain, redness, or swelling at the site of the IV or IM injection is very common. This usually resolves shortly after the infusion ends or the needle is removed.
• Gastrointestinal Upset: Mild diarrhea, nausea, or an upset stomach may occur as the antibiotic affects the natural balance of bacteria in the gut. These symptoms are typically transient.
• Oral Thrush or Vaginal Yeast Infection: Because Penicillin G kills beneficial bacteria along with harmful ones, an overgrowth of Candida (yeast) can occur, leading to white patches in the mouth or vaginal itching and discharge.

• Electrolyte Imbalance: Because Penicillin G Potassium contains significant amounts of potassium, some patients may experience a mild increase in blood potassium levels. This may cause a metallic taste in the mouth or minor muscle aches.
• Skin Rash: A mild, non-itchy rash may develop during the first week of treatment. This should still be reported to a doctor to rule out a developing allergy.
• Fever: A low-grade fever may occur as the body responds to the infection being treated or the medication itself.

• Jarisch-Herxheimer Reaction: This is a specific reaction that occurs most commonly when treating syphilis. As the bacteria die off rapidly, they release toxins into the bloodstream. Symptoms include fever, chills, headache, muscle pain, and an intensification of skin lesions. It usually occurs within 2 to 12 hours of the first dose and subsides within 24 hours.
• Hemolytic Anemia: A condition where red blood cells are destroyed faster than they can be made, often triggered by an immune response to the drug.
• Interstitial Nephritis: An inflammation of the kidneys that can lead to reduced urine output and kidney dysfunction.

> Warning: Stop taking Penicillin G and call your doctor immediately if you experience any of these.

• Anaphylaxis (Severe Allergic Reaction): This is a life-threatening emergency. Symptoms include hives, difficulty breathing, swelling of the face, lips, or tongue, and a rapid drop in blood pressure (fainting).
• Seizures: High doses of Penicillin G, especially in patients with kidney failure, can cross the blood-brain barrier and cause convulsions.
• Clostridioides difficile-Associated Diarrhea (CDAD): This is a severe form of diarrhea caused by a toxin-producing bacterium. Symptoms include watery or bloody stools, severe stomach cramps, and fever. It can occur during treatment or up to two months after stopping the antibiotic.
• Severe Hyperkalemia: Symptoms include an irregular heartbeat, extreme muscle weakness, or a 'pins and needles' sensation in the hands and feet.
• Pseudomembranous Colitis: Severe inflammation of the colon that requires immediate medical intervention.

With prolonged use (weeks or months), Penicillin G can lead to:

• Superinfections: The development of infections caused by organisms resistant to penicillin, such as certain fungi or resistant bacteria.
• Bone Marrow Suppression: Rare cases of leukopenia (low white blood cells) or thrombocytopenia (low platelets) have been reported with long-term, high-dose therapy. Regular blood monitoring is usually performed during extended treatment cycles.

There are no specific FDA Black Box Warnings for Penicillin G Potassium. However, there is a critical Warning regarding the related form, Penicillin G Benzathine, stating it must NEVER be given intravenously, as it has caused cardiac arrest and death. For Penicillin G Potassium, the primary safety focus is on hypersensitivity and neurotoxicity.

Report any unusual symptoms to your healthcare provider. Early detection of side effects is key to preventing complications.

Penicillin G Potassium is a potent medication that requires careful clinical oversight. The most critical safety consideration is the patient's allergy history. A history of even a mild rash with any penicillin-class drug (including Amoxicillin or Ampicillin) must be disclosed to the healthcare provider, as a subsequent exposure can lead to fatal anaphylaxis. Furthermore, because this drug is administered as a potassium salt, patients with pre-existing heart or kidney conditions must be monitored for electrolyte shifts.

No FDA black box warnings for Penicillin G Potassium. (Note: As mentioned previously, the 'Do Not Give IV' warning applies specifically to the Benzathine and Procaine salt forms, not the Potassium form).

• Allergic Reactions / Anaphylaxis Risk: Serious and occasionally fatal hypersensitivity reactions have been reported. These are more likely to occur in individuals with a history of penicillin hypersensitivity or a history of sensitivity to multiple allergens. Cross-reactivity with cephalosporins (like Cephalexin or Rocephin) occurs in approximately 10% of penicillin-allergic patients.
• Neurotoxicity: High blood levels of Penicillin G can cause central nervous system irritation, leading to confusion, hallucinations, and seizures. This risk is highest in patients receiving very high doses (e.g., for neurosyphilis) or those with impaired kidney function.
• Hyperkalemia (High Potassium): Each million units of Penicillin G Potassium contains about 1.7 mEq of potassium. In patients receiving 20 million units a day, this adds 34 mEq of potassium to their daily intake. This can be dangerous for patients with renal failure or those taking potassium-sparing diuretics.
• C. diff-Associated Diarrhea: Nearly all antibiotics can cause CDAD. If you develop severe diarrhea, do not use anti-diarrheal products (like Loperamide) without consulting a doctor, as these can trap toxins in the colon and worsen the condition.

Patients receiving Penicillin G Potassium typically undergo the following monitoring:

• Renal Function Tests: Periodic checks of serum creatinine and BUN (Blood Urea Nitrogen) to ensure the kidneys are clearing the drug effectively.
• Electrolyte Panels: Monitoring potassium and sodium levels, especially in patients with heart or kidney disease.
• Complete Blood Count (CBC): To check for rare effects on white blood cells or platelets during long-term therapy.
• Neurological Assessment: Monitoring for signs of twitching or mental status changes that might precede a seizure.

Penicillin G itself does not typically cause drowsiness. However, the underlying infection (like meningitis) or rare side effects like confusion or seizures can significantly impair the ability to drive. Patients should consult their doctor about when it is safe to resume these activities.

There is no direct chemical interaction between alcohol and Penicillin G. However, alcohol can dehydrate the body, strain the liver, and weaken the immune system, all of which can hinder the body's ability to fight a serious infection. It is generally recommended to avoid alcohol until the infection has fully cleared.

It is vital to complete the entire course of Penicillin G as prescribed. Stopping the medication early, even if you feel better, can allow the remaining bacteria to multiply and develop resistance to the drug. This makes future infections much harder to treat. There is no 'withdrawal' syndrome associated with Penicillin G, but the 'rebound' of an untreated infection is a significant risk.

> Important: Discuss all your medical conditions with your healthcare provider before starting Penicillin G, especially if you have asthma, hay fever, or kidney disease.

While few drugs are strictly contraindicated with Penicillin G, the following combinations are avoided due to severe risks:

• Live Typhoid Vaccine: Antibiotics like Penicillin G can kill the live bacteria in the vaccine, making it ineffective. The vaccine should be administered at least 24 hours after the last dose of the antibiotic.
• BCG Vaccine (Intravesical): Similar to the typhoid vaccine, Penicillin G can reduce the efficacy of the BCG treatment for bladder cancer.

• Probenecid: This medication is often used for gout, but it also blocks the renal tubular secretion of Penicillin G. While sometimes used intentionally to increase penicillin levels in the blood, it can also lead to toxicity if not carefully managed.
• Methotrexate: Penicillin G can interfere with the body's ability to clear Methotrexate (used for cancer and rheumatoid arthritis), leading to dangerously high levels of Methotrexate in the blood and severe side effects like bone marrow suppression.
• Potassium-Sparing Diuretics (e.g., Spironolactone, Triamterene): Using these alongside Penicillin G Potassium significantly increases the risk of life-threatening hyperkalemia (excessive potassium).

• Bacteriostatic Antibiotics (e.g., Tetracyclines, Erythromycin): Because Penicillin G works by killing bacteria that are actively growing, 'bacteriostatic' drugs that merely stop bacterial growth can interfere with Penicillin G’s bactericidal action. It is generally recommended to avoid using these together unless specifically directed by an infectious disease specialist.
• Oral Contraceptives: Some studies suggest that antibiotics may slightly reduce the effectiveness of birth control pills by altering gut flora. While the risk is low, healthcare providers often recommend using a backup method of contraception (like condoms) during antibiotic therapy.
• Warfarin (Blood Thinners): Antibiotics can change the bacterial flora in the gut that produces Vitamin K. This can enhance the effect of Warfarin, increasing the risk of bleeding. More frequent monitoring of the INR (International Normalized Ratio) is required.

Since Penicillin G Potassium is administered by injection, food does not affect its absorption. However, patients should maintain adequate hydration to help the kidneys process and excrete the medication and the potassium load.

• Potassium Supplements: Avoid taking extra potassium unless specifically directed by your doctor, as the medication already provides a significant amount.
• Kava Kava / Valerian: While no direct interaction exists, these herbs can cause drowsiness, which might complicate the monitoring for neurological side effects of Penicillin G.

Penicillin G can cause false-positive results in certain laboratory tests:

• Urine Glucose Tests: It may cause a false-positive result with copper reduction tests (e.g., Benedict's solution or Clinitest). Use glucose enzymatic tests (like Clinistix) instead.
• Coombs Test: It can cause a positive direct antiglobulin test, which might be mistaken for other blood disorders.
• Protein Tests: High concentrations of penicillin in the urine can interfere with some protein measurement techniques.

> Important: Tell your doctor about ALL medications, supplements, and herbal products you are taking. This includes over-the-counter pain relievers and vitamins.

Penicillin G Potassium must NEVER be used in the following circumstances:

1. 1Proven Penicillin Allergy: Any patient with a documented history of anaphylaxis, angioedema (swelling), or severe hives in response to any penicillin is strictly prohibited from receiving the drug. The risk of a fatal reaction outweighs any potential benefit.
2. 2Previous Severe Reaction to Cephalosporins: If a patient has had a life-threatening reaction to a cephalosporin, the risk of cross-sensitivity is too high to safely administer Penicillin G.

Conditions requiring careful risk-benefit analysis include:

• Severe Renal Failure: While not an absolute contraindication, the risk of seizures and hyperkalemia is extremely high. If Penicillin G must be used, the dose must be drastically reduced and the patient must be monitored in an ICU setting.
• Congestive Heart Failure (CHF): The potassium load from the medication can cause fluid retention and heart rhythm issues in patients with weakened hearts. Penicillin G Sodium may be a preferred alternative in these cases.
• Asthma or Significant Allergies: Patients with a history of multiple environmental allergies or asthma are statistically more likely to experience a severe allergic reaction to penicillin.

Patients should be aware of cross-sensitivity between Penicillin G and the following classes:

• Cephalosporins: (e.g., Cephalexin, Ceftriaxone, Cefepime). Approximately 1% to 10% of patients allergic to penicillin will also react to these.
• Carbapenems: (e.g., Meropenem, Imipenem). There is a documented risk of cross-reactivity, though it is generally lower than with cephalosporins.
• Monobactams: (e.g., Aztreonam). This is generally considered safe for penicillin-allergic patients, as it has a different molecular structure.

> Important: Your healthcare provider will evaluate your complete medical history, including any past rashes or breathing issues with medications, before prescribing Penicillin G.

FDA Pregnancy Category B.

Penicillin G has been used extensively in pregnant women for decades, particularly for the treatment of syphilis and the prevention of Group B Streptococcus transmission to the newborn. Animal studies have shown no evidence of impaired fertility or harm to the fetus. In humans, Penicillin G crosses the placenta, but there is no evidence of an increased risk of birth defects or other adverse fetal outcomes. It is considered the drug of choice for treating syphilis during pregnancy to prevent congenital syphilis in the infant. However, like all medications, it should be used during pregnancy only if clearly needed.

Penicillin G is excreted into human breast milk in small amounts. While generally considered compatible with breastfeeding by the American Academy of Pediatrics, there are three potential risks to the nursing infant:

1. 1Sensitization: The infant could develop an allergy to penicillin.
2. 2Diarrhea/Thrush: The infant's gut flora may be altered, leading to diarrhea or oral yeast infections.
3. 3Rash: The infant may develop a mild skin rash.

Healthcare providers typically advise mothers to monitor their infants for these signs while receiving treatment.

Penicillin G is approved for use in infants and children, including neonates. It is a critical tool in treating neonatal syphilis and bacterial meningitis. Because pediatric kidney function is not fully developed (especially in premature infants), dosing must be meticulously calculated by weight and age. Growth and development are not known to be affected by short-term use of Penicillin G.

Clinical studies of Penicillin G did not include sufficient numbers of subjects aged 65 and over to determine if they respond differently than younger subjects. However, it is well-known that elderly patients are more likely to have decreased renal function. Because the risk of toxic reactions (like seizures) and hyperkalemia is greater in patients with impaired renal function, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, and kidney function should be monitored closely.

Patients with a GFR (Glomerular Filtration Rate) below 50 mL/min require dose adjustments.

• Mild (GFR 10-50 mL/min): Dosing interval may be extended to every 8-12 hours.
• Severe (GFR <10 mL/min): Dose is typically reduced to 25% of the standard dose, or the interval is extended to every 12-24 hours.
• Dialysis: Penicillin G is removed by hemodialysis. A supplemental dose is usually given after each session.

Isolated liver disease does not significantly change the clearance of Penicillin G. However, in the rare 'hepatorenal syndrome' where both organs are failing, the half-life of the drug can extend to 10 hours or more, necessitating extreme caution and frequent blood level monitoring if available.

> Important: Special populations require individualized medical assessment and frequent monitoring by a clinical pharmacist or physician.

Penicillin G Potassium is a bactericidal antibiotic that inhibits the synthesis of the bacterial cell wall. It targets the final stage of peptidoglycan synthesis by binding to Penicillin-Binding Proteins (PBPs) located on the inner surface of the bacterial cell membrane. These PBPs are enzymes (transpeptidases, carboxypeptidases, and endopeptidases) that catalyze the cross-linking of the peptidoglycan chains. By inactivating these enzymes, Penicillin G prevents the formation of a rigid cell wall. Without this wall, the high internal osmotic pressure of the bacterium causes it to take in water and eventually burst (lysis). This action is highly specific to bacteria because human cells do not possess a cell wall or peptidoglycan.

Penicillin G exhibits time-dependent killing. This means that its efficacy is best predicted by the amount of time the concentration of the drug in the blood remains above the Minimum Inhibitory Concentration (MIC) for the specific bacteria being treated. Unlike some antibiotics that work better with higher peak concentrations, Penicillin G works best when a steady, consistent level is maintained. This is why it is often given in frequent doses (every 4 hours) or via continuous infusion.

| Parameter | Value |

|---|---|

| Bioavailability | N/A (Administered IV/IM) |

| Protein Binding | 45% to 65% (primarily Albumin) |

| Half-life | 30 to 50 minutes (Normal Renal Function) |

| Tmax | 15-30 minutes (IM); Immediate (IV) |

| Metabolism | Minimal (15-30% as inactive metabolites) |

| Excretion | Renal (60-90% unchanged in urine) |

• Molecular Formula: C16H17KN2O4S
• Molecular Weight: 372.48 g/mol
• Solubility: Highly soluble in water and isotonic saline.
• Structure: Contains the characteristic four-membered beta-lactam ring fused to a five-membered thiazolidine ring. The 'G' stands for the benzyl side chain attached to the 6-aminopenicillanic acid nucleus.

Penicillin G is the prototypical 'Natural Penicillin.' It is the reference standard against which all other beta-lactam antibiotics are measured. Related medications in this class include Penicillin V (the oral form) and the semi-synthetic penicillins like Amoxicillin, though the latter have a broader spectrum of activity against Gram-negative bacteria.