Benzapen12 lac units/vial

Streptococcal Infections

Benzapen is an established, FDA-approved treatment for infections caused by susceptible group A beta-hemolytic streptococci, such as streptococcal pharyngitis/tonsillitis ("strep throat") and mild-to-moderate skin and soft-tissue infections due to susceptible Streptococcus pyogenes. It is given as a single intramuscular injection for uncomplicated streptococcal upper respiratory infection.

Rheumatic Fever and Glomerulonephritis Prophylaxis

Benzapen is guideline-supported (American Heart Association) for long-term secondary prophylaxis against recurrence of rheumatic fever and for prophylaxis of acute glomerulonephritis following streptococcal infection, given as a periodic intramuscular injection over a period of years.

Syphilis

Benzapen is an established, first-line, guideline-supported (CDC) treatment for syphilis caused by Treponema pallidum, including primary, secondary, and early latent syphilis (single dose), and late latent syphilis or syphilis of unknown duration (three weekly doses). Benzapen is also indicated for congenital syphilis in infants under specific dosing protocols. Benzapen is not adequate treatment for neurosyphilis, because it does not reliably achieve treponemicidal concentrations in cerebrospinal fluid; a different, higher-penetrating penicillin regimen is required for neurosyphilis.

Yaws and Other Susceptible Treponemal Infections

Benzapen is the World Health Organization-recommended treatment for yaws (endemic treponematosis) as part of global eradication efforts, typically as a single intramuscular dose.

Benzapen is not effective against penicillinase-producing organisms, gram-negative bacteria, or infections requiring rapid attainment of high, sustained serum antibiotic levels, given its slow-release depot nature.

Each intramuscular injection (vial or prefilled syringe) contains Benzathine Penicillin as a sterile aqueous suspension, commonly available in strengths of 600,000 units, 1,200,000 units, and 2,400,000 units per dose, depending on the marketed presentation.

Benzapen is a long-acting ("depot") injectable form of natural penicillin G, formed by combining penicillin G with the poorly soluble base benzathine. After deep intramuscular injection, Benzapen is slowly hydrolyzed and released from the injection site into the bloodstream, producing low but sustained serum penicillin levels for two to four weeks or longer from a single dose. Because of this prolonged action, Benzapen is used mainly for infections caused by organisms that remain highly susceptible to penicillin and do not require high peak drug concentrations, most notably certain streptococcal infections and syphilis. Benzapen must be given only by deep intramuscular injection and must never be given intravenously.

Long-acting (depot) natural penicillin; Beta-lactam antibiotic

Benzathine Penicillin is a natural penicillin that exerts a bactericidal effect by inhibiting bacterial cell wall synthesis. Benzathine Penicillin (via its active penicillin G moiety) binds to penicillin-binding proteins (PBPs) located on the bacterial cell membrane, inhibiting the transpeptidation step of peptidoglycan cross-linking. This weakens the cell wall, leading to osmotic instability, lysis, and death of actively dividing susceptible bacteria, including Streptococcus pyogenes and Treponema pallidum.

Unlike aqueous penicillin G, which is absorbed and eliminated rapidly, Benzathine Penicillin is a depot formulation: following deep intramuscular injection, it forms a local reservoir from which penicillin G is released slowly and continuously over an extended period, producing low but persistent serum concentrations for two to four weeks (sometimes longer) after a single dose. This pharmacokinetic profile makes Benzathine Penicillin unsuitable for infections requiring high or rapidly attained serum levels, but well suited to prolonged, intermittent-dosing prophylaxis and to organisms, like T. pallidum, that remain exquisitely susceptible to sustained low-level penicillin exposure. Elimination is primarily renal, via tubular secretion and glomerular filtration of the released penicillin G.

• Benzapen must be given only by deep intramuscular injection into a large muscle (upper outer buttock in adults; mid-lateral thigh preferred in infants and young children).
• Benzapen must never be given intravenously; inadvertent intravascular or intra-arterial injection has been associated with serious, sometimes fatal, embolic-type reactions with cardiopulmonary and neurologic symptoms.
• Before injecting, the person administering Benzapen should aspirate (draw back on the syringe plunger) to confirm the needle is not in a blood vessel.
• The suspension should be brought to room temperature and shaken well immediately before use to ensure a uniform suspension, and administered promptly using an adequately sized needle.
• Because Benzapen is a depot injection that can cause local pain, injection sites should be rotated for patients receiving repeated doses (such as rheumatic fever prophylaxis).
• Facilities and personnel prepared to manage acute anaphylaxis should be available whenever Benzapen is administered, given its prolonged duration of action.
• Complete the full prescribed course/injection schedule of Benzapen for the specific infection being treated; do not stop, extend, skip doses, or share this medicine with others without medical advice.

• Probenecid: decreases renal tubular secretion of penicillin, increasing and prolonging serum concentrations of Benzapen; this combination is sometimes used deliberately under medical supervision but can also increase the risk of penicillin-related side effects.
• Tetracyclines and other bacteriostatic antibiotics: may antagonize the bactericidal action of Benzapen by slowing bacterial growth; concurrent use is generally avoided when treating an active infection.
• Methotrexate: penicillins, including Benzapen, may reduce renal clearance of methotrexate, increasing the risk of methotrexate toxicity; concurrent use requires caution and monitoring.
• Oral typhoid vaccine: concurrent antibiotic use, including Benzapen, may reduce the immune response to live oral typhoid vaccine; vaccination should generally be separated from antibiotic therapy.

Common Side Effects

• Pain, redness, swelling, or induration at the injection site (common with this depot formulation)
• Sterile abscess or nodule formation at the injection site
• Mild rash or urticaria

Serious Side Effects (Seek Medical Attention)

• Signs of a severe allergic/anaphylactic reaction, such as swelling of the face, lips, tongue, or throat, difficulty breathing, wheezing, or sudden drop in blood pressure — see Contraindications and Precautions and Warnings
• Severe or widespread skin reactions, including blistering or peeling skin
• Neurologic symptoms (such as severe anxiety, confusion, hallucinations, seizure, or a sense of impending doom) or cardiopulmonary symptoms (such as chest pain or difficulty breathing) occurring immediately after injection, which may indicate an inadvertent intravascular/embolic-type reaction — see Precautions and Warnings
• Fever, chills, muscle aches, or worsening symptoms shortly after the first dose when Benzapen is used for syphilis, which may represent a Jarisch-Herxheimer reaction rather than a drug allergy — see Precautions and Warnings
• Severe or persistent diarrhea, which may indicate Clostridioides difficile-associated diarrhea or colitis

Pregnancy

Benzapen has a long history of clinical use in pregnancy, and penicillin is generally considered the preferred and, for syphilis, the only well-established effective treatment in pregnant women, because untreated maternal syphilis carries a very high risk of transmission to the fetus and serious congenital harm. Nonetheless, as with any medicine in pregnancy, Benzapen should be used only if clearly needed and if the potential benefit justifies the potential risk to the fetus; use of Benzapen in pregnancy should always be under the direct guidance of a physician. Pregnant patients treated with Benzapen for syphilis should be counseled about the possibility of a Jarisch-Herxheimer reaction, which can occasionally be associated with preterm labor or fetal distress and warrants monitoring.

Breastfeeding

Penicillins, including Benzapen, pass into breast milk in small amounts. Benzapen is generally considered compatible with breastfeeding, but the nursing infant should be observed for possible effects such as diarrhea, rash, or thrush, and a physician should be consulted before use of Benzapen while breastfeeding.

• Not for intravenous use: Benzapen must be given only by deep intramuscular injection. Inadvertent intravenous, intra-arterial, or perivascular injection of Benzapen has been associated with serious and sometimes fatal reactions, including cardiac arrest, cardiorespiratory arrest, and neurologic symptoms consistent with an embolic-type event; strict adherence to proper deep intramuscular injection technique, including aspiration before injection, is essential.
• Anaphylaxis and serious hypersensitivity reactions: penicillins are a well-recognized cause of severe, potentially fatal allergic reactions. Facilities and personnel prepared to manage acute anaphylaxis should be available whenever Benzapen is administered, particularly given the prolonged duration of action of this depot formulation, which can prolong the course of a reaction. Careful screening for prior penicillin/cephalosporin allergy before administration is essential; see Contraindications.
• Jarisch-Herxheimer reaction: a transient reaction (fever, chills, headache, myalgia, and sometimes worsening of skin lesions) can occur within hours of starting antibiotic treatment for syphilis and other spirochetal infections, including with Benzapen. This reaction is not a drug allergy and generally resolves within 24 hours; patients being treated for syphilis should be counseled about this possibility in advance.
• Injection-site reactions: pain, induration, and sterile abscess/nodule formation are common with the depot nature of Benzapen; rotating injection sites is recommended for patients receiving repeated doses.
• Antibiotic stewardship: take Benzapen exactly as prescribed by your physician; do not stop, extend, skip doses, or share this medicine with others without medical advice. Completing the full prescribed schedule is essential both for cure and to limit the development of antibiotic resistance.
• Alternative therapy in penicillin-allergic patients: patients with a confirmed penicillin allergy who require treatment for an infection normally treated with Benzapen (for example, syphilis) need an alternative antibiotic regimen; in situations such as pregnancy, where penicillin is generally preferred for syphilis, specialist guidance on desensitization or alternative regimens should be sought rather than substituting a less-established therapy.
• Renal impairment: use with caution in patients with significant renal impairment, since accumulation of penicillin can occur; see Use in Special Populations.

Specific data on Benzapen overdose are limited because of its slow-release depot formulation, but excessive doses of penicillins can cause neuromuscular hyperexcitability, including confusion, twitching, or seizures, particularly in patients with renal impairment where clearance of penicillin is reduced. There is no specific antidote for Benzapen overdose; because Benzapen is a slow-release intramuscular depot, its effects cannot be rapidly reversed once injected. If an overdose or an unusual reaction following administration of Benzapen is suspected, seek immediate medical attention or contact emergency services/a poison control center; management is supportive and symptomatic, and hemodialysis is not effective at removing Benzapen once it has been injected as a depot.

Store Benzapen suspension for injection at room temperature (below 30°C), protected from freezing, excessive heat, and light. Do not freeze the suspension. Shake well before use to ensure a uniform suspension, and use only if the suspension can be evenly resuspended. Keep Benzapen out of the reach and sight of children, and follow the specific storage instructions on the product label, as these can vary between manufacturers.

Pediatric Patients

Benzapen is used in children for streptococcal infections, rheumatic fever/glomerulonephritis prophylaxis, congenital syphilis, and yaws, using weight-based dosing as outlined in the dosage table above. Safety and efficacy for indications and age groups outside these well-established uses have not been established, and pediatric dosing (particularly for congenital syphilis) should be guided by a pediatric infectious disease specialist.

Elderly

No specific dose adjustment of Benzapen is established for older adults based on age alone; however, elderly patients are more likely to have reduced renal function, so renal status should be considered, and patients should be assessed for muscle mass adequate for safe deep intramuscular injection.

Renal Impairment

Benzapen is eliminated mainly via the kidneys. Since its slow-release depot nature already produces low sustained serum levels, significant renal impairment can lead to accumulation and increased risk of toxicity (including neuromuscular irritability); use with caution and under close medical supervision in patients with significant renal impairment.

Hepatic Impairment

No specific dose adjustment of Benzapen is established for hepatic impairment, as penicillins are not significantly metabolized by the liver; standard dosing is generally used, with routine clinical monitoring.

Pregnant and Breastfeeding Women

See the Pregnancy and Lactation section above for detailed guidance on the use of Benzapen in this population.

Duration of therapy with Benzapen depends entirely on the indication: a single intramuscular injection is used for streptococcal pharyngitis and for primary/secondary/early latent syphilis; three weekly injections (three weeks total) are used for late latent syphilis or syphilis of unknown duration; and for secondary prophylaxis of rheumatic fever, injections are repeated every 3–4 weeks for a period of years, often into adulthood, based on individual recurrence risk as determined by a physician. Patients should complete the full prescribed schedule of Benzapen and should not stop, extend, or repeat treatment without medical advice.

Natural penicillins; Beta-lactam antibiotics; Long-acting depot penicillin

Benzathine Penicillin is a bactericidal antibiotic. After slow release of penicillin G from the intramuscular depot, it diffuses to bacterial cells and binds to penicillin-binding proteins (transpeptidases) on the bacterial cell membrane, inhibiting the final cross-linking (transpeptidation) step of peptidoglycan synthesis required for bacterial cell wall integrity. This weakens the growing cell wall, causing osmotic lysis and death of actively multiplying susceptible organisms such as Streptococcus pyogenes and Treponema pallidum.

B

Benzapen is used in pediatric patients for weight-based dosing of streptococcal pharyngitis/skin infections (300,000–600,000 units IM as a single dose for children under 27 kg; 1,200,000 units for those 27 kg or more), for rheumatic fever/glomerulonephritis secondary prophylaxis (1,200,000 units IM every 3–4 weeks, continued for years per cardiology guidance), and for congenital syphilis (50,000 units/kg IM as a single dose, only under specialist pediatric infectious disease protocols after excluding neurosyphilis). Safety and efficacy of Benzapen for uses and age groups outside these established indications have not been established. As in adults, Benzapen must be given by deep intramuscular injection only, using an appropriate injection site (mid-lateral thigh is generally preferred in infants and young children), and facilities for managing anaphylaxis should be available.