Procaine- benzyl penicillin (Penicillin G)

Procaine-benzylpenicillin belongs to the pharmacological class of Beta-Lactam Antibiotics.

Procaine-benzylpenicillin has been approved to relieve symptoms and also for the treatment and maintenance of Streptococcal infection,Pneumococcal infection,Staphylococcal infection,Syphilis,Gonorrhea, Actinomycosis and Anthrax.

After intramuscular injection, procaine benzylpenicillin is rapidly absorbed and reaches its peak plasma concentration within 15 to 30 minutes. The half-life of benzylpenicillin is approximately 30 minutes, and the half-life of procaine is about 1 to 2 hours. Procaine benzylpenicillin is widely distributed throughout the body, including into the cerebrospinal fluid (CSF) and placenta. It is found to be primarily excreted unchanged in the urine by the glomerular filtration and active tubular secretion.

The common side effects involving the use of Procaine-benzylpenicillin are allergic reactions, gastrointestinal upset, and hematological effects.

Procaine-benzylpenicillin is available in the form of Intramuscular or Subcutaneous.

Procaine-benzylpenicillin is approved in the U.S., U.K., Germany, Japan, Malaysia, India, and China.

Procaine- benzylpenicillin belongs to the pharmacological class of Beta-Lactam Antibiotics.

Procaine- benzylpenicillin is a beta-lactam antibiotic that works by inhibiting the growth of bacterial cell walls. It binds to penicillin-binding proteins (PBPs) in the bacterial cell wall, interfering with the cross-linking of peptidoglycan chains, ultimately leading to cell death.

Procaine- benzylpenicillin has been approved to relieve symptoms and also for the treatment and maintenance of Streptococcal infection, Pneumococcal infection, Staphylococcal infection, Syphilis, Gonorrhea, Actinomycosis, and Anthrax.

When given intramuscularly, the Cmax for procaine is reached within 15-30 minutes, while the Cmax for benzylpenicillin is reached within 30-60 minutes. The Tmax for procaine is around 30-45 minutes, and the Tmax for benzylpenicillin is around 45-90 minutes.

The duration of action of procaine- benzylpenicillin is relatively long, with a half-life of about 30 minutes for procaine and about 60 minutes for benzylpenicillin. This allows for once-daily dosing in some cases.

Procaine-benzyl penicillin is available in the form of Intramuscular or Subcutaneous.

Procaine- benzylpenicillin can be used in the following treatment:

• Streptococcal infections
• Pneumococcal infections
• Staphylococcal infections
• Syphilis
• Gonorrhea
• Actinomycosis
• Anthrax

Procaine-benzylpenicillin can help to relieve symptoms and also for the treatment and maintenance of Streptococcal infection, Pneumococcal infection, Staphylococcal infection, Syphilis, Gonorrhea, Actinomycosis, and Anthrax.

Procaine-benzylpenicillin is approved for use in the following clinical indications:

• Streptococcal infections
• Pneumococcal infections
• Staphylococcal infections
• Syphilis
• Gonorrhea
• Actinomycosis
• Anthrax

Streptococcal Infections: The recommended dosage for adults is 1.2 to 2.4 million units IM every 24 hours for ten days. For pediatric patients, the recommended dosage is 25,000 to 50,000 units per kg body weight every 24 hours for ten days.

Pneumococcal Infections: The recommended dosage for adults is 1.2 to 2.4 million units IM every 24 hours for 10 to 14 days. For pediatric patients, the recommended dosage is 50,000 to 100,000 units per kg body weight every 24 hours for 10 to 14 days.

Syphilis: The recommended dosage for adults is 2.4 million units IM once per week for three weeks.

Gonococcal Infections: The recommended dosage for adults is 2.4 million units of IM as a single dose.

Streptobacillary Rat Bite Fever: The recommended dosage for adults is 900,000 units IM every 12 hours for 7 to 10 days. For pediatric patients, the recommended dosage is 50,000 units per kg body weight every 12 hours for 7 to 10 days.

Lyme Disease: The recommended dosage for adults is 2.4 to 4.8 million units IM every 24 hours for 14 to 21 days. For pediatric patients, the recommended dosage is 50,000 to 100,000 units per kg body weight every 24 hours for 14 to 21 days.

Diphtheria: The recommended dosage for adults is 1.2 to 2.4 million units IM every 24 hours for 14 days. For pediatric patients, the recommended dosage is 50,000 units per kg body weight every 24 hours for 14 days.

Anthrax: The recommended dosage for adults is 2.4 million units IM every 12 hours for 60 days. For pediatric patients, the recommended dosage is 50,000 units per kg body weight every 12 hours for 60 days.

Procaine-benzylpenicillin is available in the form of following prefilled syringes:

• 300,000 units
• 600,000 units
• 900,000 units
• 1.2 million units
• 1.5 million units

Avoid high-acid foods like citrus fruits as well as juices like orange and grapefruit, soda, and also chocolates.

Alcohol intake might lead to vomiting, nausea, and headache.

Multivitamins and antacids which contain minerals, i.e. primarily aluminum, magnesium, calcium, iron, or zinc, which bind to the antibiotic as well as refrain it from working. Spacing them at least for 2 hours after Procaine-benzylpenicillin administration is recommended.

Procaine-benzylpenicillin may is contraindicated under the following conditions:

• Procaine-benzylpenicillin is contraindicated in patients who have a history of hypersensitivity or allergic reactions to penicillins or other beta-lactam antibiotics. The drug Procaine Benzyl Penicillin should not be used in patients with a history of severe hypersensitivity reactions (e.g. anaphylaxis) to procaine or other local anesthetics.

• Additionally, procaine-benzylpenicillin should be used with caution or avoided in patients with a history of renal impairment, as the drug is primarily excreted by the kidneys and may accumulate in patients with impaired renal function. It should also be used with caution in patients with a history of bleeding disorders, as procaine can interfere with platelet function and cause bleeding.
• Patients with a history of gastrointestinal disease or pseudomembranous colitis associated with antibiotic use
• Patients with a history of methemoglobinemia or other blood disorders
• Patients who have a history of seizures or other neurological disorders
• Patients who have a history of liver disease or impaired liver function.

The physician should closely monitor the patients as well as keep pharmacovigilance as follows:

Anaphylaxis

Allergic reactions: Patients with a history of hypersensitivity reactions to penicillin or other beta-lactam antibiotics should not use procaine-benzylpenicillin. Anaphylactic reactions may occur, and immediate treatment is necessary. Patients should be closely monitored for the allergic reactions during treatment.

Severe cutaneous adverse reactions

Severe cutaneous adverse reactions (SCARs) associated with procaine benzylpenicillin are rare but can occur. SCARs are severe allergic reactions that affect the skin and can also involve other organs. The most common types of SCARs associated with procaine benzylpenicillin are:

• Stevens-Johnson syndrome (SJS)
• Toxic epidermal necrolysis (TEN)
• Drug reaction with eosinophilia and systemic symptoms (DRESS)

SJS and TEN are the most severe types of SCARs and are considered medical emergencies. They are characterized by the development of painful skin lesions, blisters, and mucosal involvement, including the eyes, mouth, and genitals. The skin may also peel off in sheets, leading to extensive areas of denuded skin. SJS and TEN can be life-threatening and require immediate medical attention.

DRESS syndrome is a less severe type of SCAR that usually develops 2-6 weeks after starting treatment with procaine benzylpenicillin. Symptoms of DRESS syndrome may include fever, rash, lymphadenopathy, and organ involvement, such as hepatitis, pneumonitis, or nephritis.

Patients with a history of allergic reactions to penicillin or other beta-lactam antibiotics are at increased risk of developing SCARs with procaine benzylpenicillin. The risk of SCARs may also be increased in patients with certain genetic markers, such as HLA-B*57:01.

If a patient develops a skin rash or any other symptoms of an allergic reaction during treatment with procaine benzylpenicillin, they should seek medical attention immediately. Treatment with procaine benzylpenicillin should be discontinued, and alternative antibiotics should be considered.

Methemoglobinemia

Methemoglobinemia is a rare but potentially serious adverse reaction associated with the use of procaine-benzylpenicillin. Methemoglobinemia is a condition in which the iron in hemoglobin is oxidized to the ferric state, leading to reduced oxygen-carrying capacity of the blood.

Procaine-benzylpenicillin can cause methemoglobinemia by oxidizing hemoglobin to methemoglobin, which cannot bind oxygen. The risk of methemoglobinemia is higher in patients with glucose-6-phosphate dehydrogenase deficiency, a genetic disorder that can lead to oxidative stress in red blood cells.

Symptoms of methemoglobinemia may include shortness of breath, cyanosis (bluish discoloration of the skin and mucous membranes), headache, dizziness, fatigue, and confusion. Severe methemoglobinemia can lead to seizures, coma, and even death.

If a patient develops symptoms of methemoglobinemia during treatment with procaine-benzylpenicillin, treatment should be stopped immediately. The patient may require supplemental oxygen, methylene blue (a medication that can reduce methemoglobin back to hemoglobin), or in severe cases, exchange transfusion (a procedure in which the patient's blood is replaced with donor blood).

Patients with a history of methemoglobinemia or glucose-6-phosphate dehydrogenase deficiency should be closely monitored when receiving procaine-benzylpenicillin, and alternative antibiotics should be considered.

A case report from 2019 described a patient who developed methemoglobinemia after receiving a single dose of intravenous procaine-benzylpenicillin for the treatment of syphilis. The patient was successfully treated with methylene blue and supportive care.

Pseudomembranous Colitis

Pseudomembranous colitis is a rare but potentially serious adverse reaction associated with the use of procaine-benzylpenicillin. Pseudomembranous colitis is an inflammation of the colon caused by overgrowth of Clostridium difficile bacteria in the gut. This overgrowth can occur as a result of disruption of the normal gut flora, which can be caused by antibiotics such as procaine-benzylpenicillin.

Symptoms of pseudomembranous colitis may include diarrhea (which may be bloody), abdominal pain, fever, and nausea. Severe cases can lead to dehydration, electrolyte imbalances, and even perforation of the colon.

If a patient develops symptoms of pseudomembranous colitis during or after treatment with procaine-benzylpenicillin, treatment should be stopped immediately. The patient may require treatment with an alternative antibiotic, and in severe cases, hospitalization and supportive care.

There have been case reports and studies documenting the association between procaine-benzylpenicillin use and pseudomembranous colitis. For example:

A case report from 2014 described a patient who developed pseudomembranous colitis after receiving intramuscular procaine-benzylpenicillin for the treatment of streptococcal pharyngitis. The patient was successfully treated with metronidazole and supportive care.

A study from 2009 evaluated the incidence of pseudomembranous colitis associated with the use of various antibiotics, including procaine-benzylpenicillin, in a hospital in the United States. The study included 30 patients with pseudomembranous colitis and found that 6 of these patients (20%) had received procaine-benzylpenicillin in the 30 days prior to the onset of symptoms. The authors concluded that procaine-benzylpenicillin is one of several antibiotics associated with an increased risk of pseudomembranous colitis.

Procaine Reactions (Hoigne’s Syndrome)

Procaine reactions, also known as Hoigne's syndrome, are a rare but potentially serious adverse reaction associated with the use of procaine-containing medications, including procaine-benzylpenicillin. Procaine reactions are characterized by a range of symptoms, including anxiety, restlessness, confusion, hallucinations, agitation, tremors, and seizures. The exact cause of procaine reactions is not well understood, but it is thought to be related to the metabolism of procaine in the body. Procaine is metabolized into para-aminobenzoic acid (PABA), which can accumulate in the body and potentially cause neurotoxicity.

Symptoms of procaine reactions typically occur within minutes to hours of administration of procaine-containing medications, and can last for several hours. The severity of symptoms can vary widely, and can range from mild agitation to severe seizures and cardiovascular collapse. If a patient develops symptoms of a procaine reaction during or after treatment with procaine-benzylpenicillin, treatment should be stopped immediately. The patient may require treatment with anticonvulsants, sedatives, and/or supportive care. There have been case reports and studies documenting the association between procaine-containing medications, including procaine-benzylpenicillin, and procaine reactions. For example:

A case report from 2018 described a patient who developed a procaine reaction after receiving intramuscular procaine-benzylpenicillin for the treatment of syphilis. The patient experienced agitation, confusion, hallucinations, and seizures, and was treated with benzodiazepines and anticonvulsants.

A study from 2017 evaluated the incidence of procaine reactions associated with the use of various procaine-containing medications in a hospital in the United States. The study included 17 patients with procaine reactions and found that 11 of these patients (65%) had received procaine-benzylpenicillin. The authors concluded that procaine-containing medications, including procaine-benzylpenicillin, should be used with caution and patients should be monitored closely for the development of procaine reactions.

Usage of alcohol should be avoided while on Procaine-benzylpenicillin medication, as alcohol might worsen the effects of any underlying disease condition, which including conditions such as blurred vision, dizziness, etc.

Procaine-benzylpenicillin is excreted in breast milk and may cause adverse effects in the nursing infant. Breastfeeding should be avoided during treatment with procaine-benzylpenicillin, or a different antibiotic may be used if possible.

Category B

Pregnancy Category B

Procaine-benzylpenicillin is generally considered safe for use during pregnancy, as it has not been associated with an increased risk of birth defects or other adverse effects in the fetus. However, as with all medications, it should be used only when clearly needed and under the supervision of a healthcare professional.

There is found to be no sufficient scientific evidence which is traceable regarding the use and safety of Procaine-benzylpenicillin in concurrent use with any particular food.

The adverse reactions related to Procaine-benzylpenicillin can be categorized as follows:

• Phlebitis
• Thrombophlebitis
• Renal tubular damage
• Interstitial nephritis
• Fever
• Rash
• Eosinophilia
• Proteinuria
• Eosinophiluria
• Hematuria
• Hyperreflexia
• Myoclonic twitches
• Seizures
• Coma
• Hyperkalemia
• Nausea
• Vomiting
• Stomatitis
• Black or hairy tongue
• Pruritus
• Fever
• Malaise
• Urticaria
• Myalgia
• Arthralgia
• Abdominal pain

The clinically relevant drug interactions of Procaine-benzylpenicillin are briefly summarized here:

• Bacteriostatic antibacterial such as chloramphenicol, erythromycins, sulfonamides or tetracyclines might antagonize the bactericidal effect of the drug penicillin, hence concurrent use of these drugs should be avoided. This has been documented in the in-vitro studies; however, the clinical significance of this interaction has not been is not well-documented.
• Penicillin blood levels might be prolonged by the concurrent administration of probenecid which blocks the renal tubular secretion of penicillin. Other drugs might compete with penicillin G for the renal tubular secretion and thus prolong the serum half-life of penicillin. These drugs are aspirin, phenylbutazone, sulfonamides, indomethacin, thiazide diuretics, furosemide and ethacrynic acid.
• Anticoagulants: Co-administration of anticoagulants and procaine-benzylpenicillin may increase the risk of bleeding. Dose adjustments may be required
• Methotrexate: Procaine-benzylpenicillin may increase the toxicity of methotrexate.
• Tetracyclines: Co-administration of tetracyclines and procaine-benzylpenicillin may decrease the effectiveness of both medications.
• Probenecid: Co-administration of probenecid and procaine-benzylpenicillin may increase the serum concentration and prolong the half-life of procaine-benzylpenicillin.

The following are the side effects involving Procaine-benzylpenicillin:

• Fever
• Swelling
• Skin rash
• Hives
• Hypersensitivity reactions
• Including chills
• Joint pain
• Weakness

Pregnancy

Pregnancy Category B

Procaine-benzylpenicillin is generally considered safe for use during pregnancy, as it has not been associated with an increased risk of birth defects or other adverse effects in the fetus. However, as with all medications, it should be used only when clearly needed and under the supervision of a healthcare professional.

Lactation

Procaine-benzylpenicillin is excreted in breast milk and may cause adverse effects in the nursing infant. Breastfeeding should be avoided during treatment with procaine-benzylpenicillin, or a different antibiotic may be used if possible.

Pediatric use

Procaine-benzylpenicillin is generally considered safe and effective for use in children, and is commonly used to treat infections in this population. However, dosages may need to be adjusted based on the age and weight of the child, and close monitoring for adverse effects is important.

Geriatric

Procaine-benzylpenicillin may be used in elderly patients, but caution should be exercised due to potential risks such as impaired renal function and increased risk of adverse effects such as allergic reactions.

Impaired renal function: Patients with impaired renal function may require dose adjustments of procaine-benzylpenicillin to prevent toxicity, as the drug is primarily eliminated through the kidneys.

Overall, the use of procaine-benzylpenicillin in specific populations should be carefully considered based on individual patient factors and the potential risks and benefits of the medication. Close monitoring for adverse effects is important in all patients.

Physicians should be knowledgeable and vigilant about the treatment and identification of overdosage of Procaine-benzylpenicillin.

An overdose of procaine-benzylpenicillin, also known as procaine penicillin or benzathine penicillin, can cause serious adverse effects and may require immediate medical attention.

Symptoms of an overdose may include severe allergic reactions, such as difficulty breathing, hives, swelling of the face, lips, tongue, or throat, seizures, confusion, hallucinations, and decreased consciousness.

In the event of an overdose, the patient should seek immediate medical attention. Treatment may include supportive care, such as respiratory support and treatment of seizures, as well as discontinuation of the medication.

It is important to note that procaine-benzylpenicillin has a narrow therapeutic index, meaning that the difference between a therapeutic dose and a toxic dose is relatively small. As such, it is important to use the medication only as prescribed by a healthcare professional, and to closely monitor patients for signs of adverse effects.

Pharmacodynamics

The pharmacodynamics of procaine-benzylpenicillin involve the inhibition of bacterial cell wall synthesis, resulting in bacterial cell death. It has a narrow spectrum of activity, and resistance can develop through several mechanisms. The dosage and administration of the drug depend on the type and severity of the infection being treated.

Pharmacokinetics

Absorption: Procaine-benzylpenicillin is administered via intramuscular injection and is absorbed slowly and incompletely into the bloodstream.

Distribution: Procaine-benzylpenicillin has a large volume of distribution, which means it is widely distributed throughout the body. It can cross the placenta and enter breast milk.

Metabolism: Procaine-benzylpenicillin is not metabolized in the body.

Elimination: Procaine-benzylpenicillin is eliminated primarily by the kidneys through urine, with a half-life of about 30 minutes for procaine and about 60 minutes for benzylpenicillin.

The pharmacokinetics of procaine-benzylpenicillin may be altered in patients with impaired kidney function, as the drug is primarily eliminated through the kidneys. The dosage of the drug may need to be adjusted in these patients to prevent toxicity.

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