Benzylpenicillin (Penicillin G)

Benzylpenicillin belongs to the pharmacological class of Beta-Lactam Antibiotics.

Benzylpenicillin has been approved to relieve symptoms and also for the treatment and maintenance of Actinomycosis (severe or extensive), Bloodstream infection, Botulism (wound), Diphtheria,, Endocarditis treatment, Leptospirosis (severe), Lyme disease, Meningitis (bacterial), Neurosyphilis, Odontogenic soft tissue infection (pyogenic), Osteomyelitis and/or discitis, Prosthetic joint infection, Rat bite fever, Skin and soft tissue infection, streptococcal, Streptococcus (maternal prophylaxis for prevention of neonatal disease), Tetanus, Toxic shock syndrome

Benzylpenicillin (penicillin G) is a narrow-spectrum antibiotic with a short half-life of approximately 30 minutes to 1 hour. After intravenous (IV) administration, the medication is rapidly absorbed and widely distributed throughout the body, including in the blood, tissues, and organs. IM administration results in slower and incomplete absorption of the medication. Benzylpenicillin is not extensively metabolized in the body and is primarily excreted unchanged by the kidneys, with approximately 60-90% of the dose excreted in the urine within 6-8 hours after administration..

The common side effects involving the use of Benzylpenicillin are Diarrhea, Nausea, Vomiting, Skin rash or hives, Fever, Joint pain or swelling, Headache, Dizziness, Fatigue, and Pain or redness at the injection site.

Benzylpenicillin is available in the form of Intramuscular and Intravenous Injections

Benzylpenicillin is approved in the Germany, Japan, Malaysia, India, U.S., U.K., and China.

Benzylpenicillin belongs to the pharmacological class of Beta-Lactam Antibiotics.

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.

Benzylpenicillin has been approved to relieve symptoms and also for the treatment and maintenance of Actinomycosis (severe or extensive), Bloodstream infection, Botulism (wound), Diphtheria,, Endocarditis treatment, Leptospirosis (severe), Lyme disease, Meningitis (bacterial), Neurosyphilis, Odontogenic soft tissue infection (pyogenic), Osteomyelitis and/or discitis, Prosthetic joint infection, Rat bite fever, Skin and soft tissue infection, streptococcal, Streptococcus (maternal prophylaxis for prevention of neonatal disease), Tetanus, Toxic shock syndrome

Given Intravenous (IV) administration the onset of action is within 15 to 30 minutes while given Intramuscular (IM) administration the onset of action is within 30 to 60 minutes. Given Intravenously ,the duration of action is approximately 4 to 6 hours, while given Intramuscularly, the the duration of action is approximately 6 to 12 hours.

Benzylpenicillin is available in the form of Intramuscular and Intravenous Injections.

Benzylpenicillin can be used in the following treatment:

• Actinomycosis, severe or extensive
• Bloodstream infection
• Botulism, wound
• Diphtheria
• Endocarditis treatment
• Leptospirosis, severe
• Lyme disease
• Meningitis, bacterial
• Neurosyphilis
• Odontogenic soft tissue infection, pyogenic
• Osteomyelitis and/or discitis
• Prosthetic joint infection
• Rat bite fever
• Skin and soft tissue infection, streptococcal
• Streptococcus, maternal prophylaxis for prevention of neonatal disease
• Tetanus
• Toxic shock syndrome

Benzylpenicillin can help to relieve symptoms and also for the treatment and maintenance of Actinomycosis (severe or extensive), Bloodstream infection, Botulism (wound), Diphtheria,, Endocarditis treatment, Leptospirosis (severe), Lyme disease, Meningitis (bacterial), Neurosyphilis, Odontogenic soft tissue infection (pyogenic), Osteomyelitis and/or discitis, Prosthetic joint infection, Rat bite fever, Skin and soft tissue infection, streptococcal, Streptococcus (maternal prophylaxis for prevention of neonatal disease), Tetanus, Toxic shock syndrome.

Benzylpenicillin is approved for use in the following clinical indications:

• Actinomycosis, severe or extensive
• Bloodstream infection
• Botulism, wound
• Diphtheria
• Endocarditis treatment
• Leptospirosis, severe
• Lyme disease
• Meningitis, bacterial
• Neurosyphilis
• Odontogenic soft tissue infection, pyogenic
• Osteomyelitis and/or discitis
• Prosthetic joint infection
• Rat bite fever
• Skin and soft tissue infection, streptococcal
• Streptococcus, maternal prophylaxis for prevention of neonatal disease
• Tetanus
• Toxic shock syndrome.

• Actinomycosis, severe or extensive: The recommended dosage is usually 1.2 to 2.4 million units every 4 to 6 hours.
• Bloodstream infection: The recommended dosage is usually 2 to 4 million units every 4 to 6 hours.
• Botulism, wound: The recommended dosage is usually 1.2 to 2.4 million units every 4 to 6 hours
• Diphtheria: The recommended dosage is usually 1.2 to 2.4 million units every 4 to 6 hours.
• Endocarditis treatment: The recommended dosage is usually 2 to 3 million units every 4 hours.
• Leptospirosis, severe: The recommended dosage is usually 1.2 to 2.4 million units every 4 to 6 hours.
• Lyme disease: The recommended dosage is usually 1.2 to 2.4 million units every 4 to 6 hours.
• Meningitis, bacterial: The recommended dosage is usually 2 to 4 million units every 4 to 6 hours.
• Neurosyphilis: The recommended dosage is usually 18 to 24 million units per day, given in divided doses.
• Odontogenic soft tissue infection, pyogenic: The recommended dosage is usually 1.2 to 2.4 million units every 4 to 6 hours.
• Osteomyelitis and/or discitis: The recommended dosage is usually 2 to 3 million units every 4 hours.
• Prosthetic joint infection: The recommended dosage is usually 2 to 3 million units every 4 hours.
• Rat bite fever: The recommended dosage is usually 1.2 to 2.4 million units every 4 to 6 hours.
• Skin and soft tissue infection, streptococcal: The recommended dosage is usually 1.2 to 2.4 million units every 4 to 6 hours.
• Streptococcus, maternal prophylaxis for prevention of neonatal disease: The recommended dosage is usually a single dose of 5 million units intravenously or intramuscularly.
• Tetanus: The recommended dosage is usually 2 to 4 million units every 4 to 6 hours.
• Toxic shock syndrome, streptococcal: The recommended dosage is usually 1.2 to 2.4 million units every 4 to 6 hours.

• Injectable solution: 300,000 units/mL, 600,000 units/mL, 1.2 million units/mL, 2.4 million units/mL, and 5 million units/mL.

Intramuscular and Intravenous Injections.

• Dosage Adjustments in Kidney Patients:

Uremic patients with CrCl >10 mL/minute/1.73 m2: Administer a usual recommended dose followed by 50% of the usual recommended dose every 4 to 5 hours.

CrCl <10 mL/minute/1.73 m2: Administer a normal dose followed by 50% of the normal dose every 8 to 10 hours.

Alternative recommendation:

GFR >50 mL/minute: No dosage adjustment necessary .

GFR 10-50 mL/minute: Administer 75% of the normal dose.

GFR <10 mL/minute: Administer 20% to 50% of the normal dose.

• Dosage Adjustments in Pediatric Patients:

Infants (up to 1 month old): The recommended dose is 50,000 to 100,000 units per kg of body weight every 12 to 24 hours.

Children (1 month to 12 years old): The recommended dose is 50,000 to 200,000 units per kg of body weight every 6 to 8 hours.

There are no specific dietary restrictions associated with the use of benzylpenicillin. However, it is important to follow your doctor's instructions regarding the timing and frequency of the medication as this can affect the absorption and effectiveness of the medication. Benzylpenicillin is often administered intravenously or intramuscularly, and in some cases, it may be given with food or fluids to help minimize potential side effects such as nausea or injection site reactions. It is also important to maintain a healthy diet and lifestyle while taking benzylpenicillin to help support your immune system and aid in the recovery process.

Benzylpenicillin may is contraindicated under the following conditions:

• Allergy to penicillin: Patients with a known allergy to penicillin or cephalosporin antibiotics should not take benzylpenicillin.
• Methicillin-resistant Staphylococcus aureus (MRSA) infection: Benzylpenicillin is not effective against MRSA infections, so it should not be used to treat these infections.
• Infectious mononucleosis: Benzylpenicillin should not be used to treat infections associated with infectious mononucleosis because it can cause a rash.
• Viral infections: Benzylpenicillin is not effective against viral infections, so it should not be used to treat these infections.
• Porphyria: Benzylpenicillin can exacerbate porphyria, a rare genetic disorder that affects the production of heme.

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

Allergic reactions: Some people may be allergic to benzylpenicillin, which can cause an allergic reaction that ranges from mild to severe. If you experience any signs of an allergic reaction, such as rash, hives, itching, difficulty breathing, or swelling of the face, lips, tongue, or throat, seek immediate medical attention.

Overgrowth of non-susceptible organisms: The use of benzylpenicillin can lead to the overgrowth of non-susceptible organisms, such as fungi, which can cause secondary infections.

Prolonged use: Prolonged use of benzylpenicillin can lead to the development of resistant strains of bacteria, which can make the medication less effective in the long run.

Interference with laboratory tests: Benzylpenicillin can interfere with some laboratory tests, such as the Coombs test, which can lead to false-positive results.

According to the US Food and Drug Administration (FDA), benzylpenicillin is excreted in breast milk in small amounts, but there is no evidence of harm to the nursing infant.

Category B

Benzylpenicillin (also known as penicillin G benzathine) is an antibiotic medication that is used to treat a variety of bacterial infections. It is classified as a category B medication for pregnancy by the US Food and Drug Administration (FDA), meaning that animal studies have not shown any adverse effects on fetal development, but there are no adequate and well-controlled studies in pregnant women. When using benzylpenicillin during pregnancy, special precautions should be taken to ensure the safety of both the mother and the fetus. Benzylpenicillin should only be used during pregnancy when the potential benefits outweigh the potential risks to the fetus. The prescribing doctor should carefully consider the risks and benefits of using this medication during pregnancy, and discuss them with the patient before prescribing.

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

The adverse reactions related to Benzylpenicillin can be categorized as follows:

Common side effects:

• Allergic reactions (rash, hives, itching, swelling, difficulty breathing)
• Gastrointestinal disturbances (diarrhea, nausea, vomiting)
• Injection site reactions (pain, redness, swelling, itching)

Less common/Rare side effects:

• Neurological side effects (confusion, seizures, encephalopathy)
• Hematological side effects (anemia, thrombocytopenia, leukopenia)
• Superinfections (candidiasis, antibiotic-resistant bacterial infections)
• Renal impairment
• Electrolyte imbalances
• Hypersensitivity reactions (fever, joint pain, eosinophilia)
• Nephritis
• Thrombophlebitis
• Hemolytic anemia
• Pseudomembranous colitis
• Stevens-Johnson syndrome
• Toxic epidermal necrolysis
• Jarisch-Herxheimer reaction (fever, chills, headache, muscle aches, tachycardia, hyperventilation)

The clinically relevant drug interactions of Benzylpenicillin are briefly summarized here:

• Probenecid: Probenecid is a medication used to treat gout and can also increase the levels of benzylpenicillin in the blood by reducing its excretion from the body. This can result in an increased risk of side effects from benzylpenicillin. Therefore, patients taking probenecid and benzylpenicillin should be closely monitored for adverse effects, and the dosage of benzylpenicillin may need to be adjusted.
• Methotrexate: Methotrexate is a medication used to treat cancer and certain autoimmune diseases, and benzylpenicillin can decrease its excretion from the body, leading to increased levels of methotrexate in the blood. This can increase the risk of methotrexate toxicity, such as bone marrow suppression and gastrointestinal toxicity. Patients taking both drugs should be closely monitored for adverse effects, and the dosage of methotrexate may need to be adjusted.
• Aminoglycosides: Aminoglycosides, such as gentamicin and tobramycin, are antibiotics that can be used to treat serious infections. Benzylpenicillin can interact with aminoglycosides, leading to decreased effectiveness of both drugs. This is because benzylpenicillin can inactivate the aminoglycosides in the bloodstream. If a patient needs to take both drugs, their healthcare provider may need to adjust the dosages or choose an alternative antibiotic.
• Tetracyclines: Tetracyclines, such as doxycycline and minocycline, are antibiotics used to treat various infections. Benzylpenicillin can interact with tetracycline antibiotics, leading to decreased effectiveness of both drugs. This is because benzylpenicillin can inactivate the tetracyclines in the bloodstream. Patients taking both drugs may need to be monitored closely for adverse effects, and the dosage of either drug may need to be adjusted.
• Oral contraceptives: Benzylpenicillin can decrease the effectiveness of oral contraceptives, increasing the risk of unintended pregnancy. This is because benzylpenicillin can interfere with the absorption and metabolism of estrogen in the body. Women taking oral contraceptives and benzylpenicillin should use a backup method of contraception, such as condoms, during treatment with benzylpenicillin and for a few days afterward.
• Warfarin: Warfarin is a blood thinner used to prevent blood clots. Benzylpenicillin can interact with warfarin, leading to an increased risk of bleeding. This is because benzylpenicillin can decrease the metabolism of warfarin in the liver, leading to increased levels of warfarin in the blood. Patients taking both drugs should be closely monitored for signs of bleeding, and the dosage of warfarin may need to be adjusted.

The following are the side effects involving Benzylpenicillin:

• Fever
• Swelling
• Skin rash
• Hives
• Hypersensitivity reactions
• Including chills
• Itching at the site of injection
• Confusion
• Anemia
• Thrombocytopenia
• Leukopenia.
• Seizures
• Encephalopathy
• Joint pain
• Weakness

• Pregnancy

Pregnancy Category B

Benzylpenicillin (also known as penicillin G benzathine) is an antibiotic medication that is used to treat a variety of bacterial infections. It is classified as a category B medication for pregnancy by the US Food and Drug Administration (FDA), meaning that animal studies have not shown any adverse effects on fetal development, but there are no adequate and well-controlled studies in pregnant women. When using benzylpenicillin during pregnancy, special precautions should be taken to ensure the safety of both the mother and the fetus. Benzylpenicillin should only be used during pregnancy when the potential benefits outweigh the potential risks to the fetus. The prescribing doctor should carefully consider the risks and benefits of using this medication during pregnancy, and discuss them with the patient before prescribing.

• Lactation

According to the US Food and Drug Administration (FDA), benzylpenicillin is excreted in breast milk in small amounts, but there is no evidence of harm to the nursing infant.

• Pediatric use

According to the US Food and Drug Administration (FDA), benzylpenicillin is generally considered safe for use in pediatric populations. However, some precautions that can be taken include:

Dosage adjustments: The dose of benzylpenicillin may need to be adjusted based on the age, weight, and medical condition of the child. The prescribing doctor should carefully consider these factors and adjust the dose accordingly.

Monitoring for allergic reactions: Allergic reactions to benzylpenicillin can occur in children. Symptoms may include rash, hives, itching, or difficulty breathing. If these symptoms occur, medical attention should be sought immediately.

Monitoring for adverse effects: While benzylpenicillin is generally considered safe in pediatric populations, it is important to monitor for any adverse effects, such as diarrhea or vomiting.

Considering alternative treatments: Depending on the medical condition being treated, there may be alternative treatments that are safer or more appropriate for use in children. Your doctor can discuss these options with you.

Precautions in newborns: In newborns, benzylpenicillin should be used with caution and only when clearly needed, as their kidneys may not yet be fully developed and may have difficulty excreting the medication from their system

Geriatric: Clinical data on the use of benzylpenicillin in geriatric populations suggest that the medication is generally well-tolerated and effective. However, there are some special precautions that should be taken when using benzylpenicillin in older adults.

Reduced renal function: Older adults may have reduced kidney function, which can affect the clearance of benzylpenicillin from the body. Dose adjustments may be needed to prevent toxicity.

Drug interactions: Older adults may be taking multiple medications, which can increase the risk of drug interactions. It is important to review the patient's medication list and monitor for potential drug interactions when prescribing benzylpenicillin.

Hypersensitivity reactions: Older adults may be more likely to experience hypersensitivity reactions to benzylpenicillin. These reactions can range from mild to severe and can include skin rash, itching, fever, and anaphylaxis. Careful monitoring is needed to identify and manage hypersensitivity reactions.

Clostridium difficile infection: Older adults are at increased risk for developing Clostridium difficile infection, which is a bacterial infection that can occur after antibiotic treatment. Benzylpenicillin can disrupt the natural balance of bacteria in the gut, increasing the risk of C. difficile infection.

Electrolyte disturbances: Benzylpenicillin can cause electrolyte disturbances, especially in older adults with underlying kidney or liver disease. Regular monitoring of electrolyte levels is needed to prevent complications.

Physicians should be knowledgeable and vigilant about the treatment and identification of overdosage of Benzylpenicillin.

Neurotoxicity: High doses of benzylpenicillin can cause neurotoxicity, which can result in seizures, confusion, agitation, and other neurological symptoms.

Nephrotoxicity: Benzylpenicillin can cause nephrotoxicity, which can result in kidney damage and impaired renal function. Patients with impaired renal function are at increased risk of experiencing nephrotoxicity from benzylpenicillin.

Electrolyte imbalances: An overdose of benzylpenicillin can cause electrolyte imbalances, which can result in abnormal heart rhythms, muscle weakness, and other symptoms.

Anaphylaxis: Benzylpenicillin is known to cause severe allergic reactions, including anaphylaxis, in some patients. An overdose of the drug can increase the risk of experiencing anaphylaxis.

Treatment for benzylpenicillin overdose typically involves supportive care and symptom management. In cases of severe overdose, hemodialysis may be necessary to remove the drug from the patient's bloodstream. Patients who experience anaphylaxis may require emergency medical treatment, such as administration of epinephrine and other supportive measures.

Pharmacodynamics

Bacterial susceptibility: Benzylpenicillin is effective against a wide range of gram-positive and some gram-negative bacteria, including Streptococcus, Staphylococcus, Neisseria, and certain strains of Escherichia coli.

Bacterial resistance: Some bacteria have developed resistance to benzylpenicillin through several mechanisms, including the production of beta-lactamases, which are enzymes that can break down the beta-lactam ring of the penicillin molecule, and alteration of the target penicillin-binding proteins.

Bactericidal activity: Benzylpenicillin exhibits bactericidal activity, meaning that it directly kills bacteria rather than simply inhibiting their growth.

Dose-response relationship: The pharmacodynamic relationship between benzylpenicillin dose and bacterial killing has been studied extensively. It is generally accepted that the rate and extent of bacterial killing increase with increasing doses of benzylpenicillin up to a certain point, beyond which no further increase in bacterial killing is observed.

Time-dependent killing: Benzylpenicillin exhibits time-dependent killing, meaning that the duration of drug exposure is more important than the peak drug concentration in determining the extent of bacterial killing.

Synergistic effects: Benzylpenicillin can exhibit synergistic effects when used in combination with other antibiotics, such as aminoglycosides. These combinations can increase the rate and extent of bacterial killing and decrease the emergence of resistance.

Overall, benzylpenicillin's pharmacodynamic properties make it an effective antibiotic medication for the treatment of a wide range of bacterial infections, though its effectiveness may be limited by the emergence of bacterial resistance.

Pharmacokinetics

• Absorption: Benzylpenicillin is administered via intravenous (IV) or intramuscular (IM) injection. When given intravenously, the drug is rapidly absorbed into the bloodstream, and its effect is immediate. When given intramuscularly, the absorption is slower, and the peak concentration is reached after about 30 to 60 minutes. The bioavailability of benzylpenicillin after intramuscular injection is approximately 37% to 76%.

• Distribution: After absorption, benzylpenicillin is distributed throughout the body. It has a low protein-binding capacity, which allows it to penetrate into tissues and organs. It can also cross the blood-brain barrier, allowing it to reach the central nervous system. The volume of distribution of benzylpenicillin is around 0.3 to 0.4 L/kg.

• Metabolism: Benzylpenicillin is not metabolized in the body. It is eliminated unchanged in the urine, and a small amount is eliminated in the bile.

• Elimination: The elimination of benzylpenicillin is dependent on the renal function of the patient. The drug is primarily eliminated by the kidneys through glomerular filtration and tubular secretion. The half-life of benzylpenicillin in adults with normal renal function is around 30 minutes to one hour. In patients with impaired renal function, the half-life can be prolonged, leading to an increased risk of toxicity.

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