Megacillin , Pentids
Classifications: antiinfective; beta-lactam antibiotic; natural penicillin
Pregnancy Category: B


1,000,000 units, 5,000,000 units, 10,000,000 units, 20,000,000 units vials; 1,000,000 units/50 mL, 2,000,000 units/50 mL 3,000,000 units/50 mL injection


Acid-labile, penicillinase-sensitive, natural penicillin. Antimicrobial spectrum is relatively narrow compared to that of the semisynthetic penicillins. Bactericidal at therapeutic serum levels; bacteriostatic at lower concentrations. Acts by interfering with synthesis of mucopeptides essential to formation and integrity of bacterial cell wall. Action is inhibited by penicillinase; therefore, penicillin G is ineffective against many strains of Staphylococcus aureus.

Therapeutic Effects

Highly active against gram-positive cocci (e.g., non-penicillinase-producing Staphylococcus, Streptococcus groups A, C, G, H, L, M, and Streptococcus pneumoniae); and gram-negative cocci (Neisseria gonorrhoeae, N. meningitidis). Also effective against gram-positive bacilli (Bacillus anthracis, Clostridium species including gas gangrene and tetanus, and certain species of Corynebacterium, Erysipelothrix, and Listeria); gram-negative bacilli (Fusobacterium, Pasteurella, Streptobacillus, and Bacteroides species). Parenteral penicillin G is effective against some strains of Salmonella and Shigella and spirochetes (Treponema pallidum, T. pertenue, Leptospira).


Moderate to severe systemic infections caused by penicillin-sensitive microorganisms: actinomycosis, anthrax, diphtheria (carrier state), empyema, erysipelas, gas gangrene, gonorrheal infections, leptospirosis, mastoiditis, meningitis, acute osteomyelitis, otitis media, pinta, pneumonia, rat-bite fever, sinus infections; certain staphylococcal infections; streptococcal infections, including scarlet fever; syphilis (all stages), tetanus, urinary tract infections, Vincent's gingivostomatitis, yaws. Also used as prophylaxis in patients with rheumatic or congenital heart disease. Since oral preparations are absorbed erratically and thus must be given in comparatively high doses, this route is generally used only for mild or stabilized infections or long-term prophylaxis.


Hypersensitivity to any of the penicillins or cephalosporins; administration of oral drug to patients with severe infections; nausea, vomiting, hypermotility, gastric dilatation; cardiospasm. Use of penicillin G sodium in patients on sodium restriction. Safety during pregnancy (category B) or lactation is not established.

Cautious Use

History of or suspected allergy (asthma, eczema, hay fever, hives); history of allergy to cephalosporins; kidney or liver dysfunction, myasthenia gravis, epilepsy, neonates, young infants. Use during lactation may lead to sensitization of infants.

Route & Dosage

Moderate to Severe Infections
Adult: PO 1.6–3.2 million U divided q6h IV/IM 1.2–24 million U divided q4h
Child: PO 25,000–100,000 U/kg divided q6h IV/IM 25,000–300,000 U/kg divided q4h

Meningococcal Meningitis
Adult: IM 1–2 million U q 2 h IV 200,000–300,000/kg/d divided q 2–4 h or 2 million to 3 million units/d by continuous infusion
Child: IV 25,000–300,000 U/kg divided q4h


Note: Check whether physician has prescribed penicillin G potassium or sodium.


PREPARE: Intermittent/Continuous: Reconstitute as for IM injection then withdraw the required dose and add to 100–1000 mL of D5W or NS IV solution, depending on length of each infusion.  

ADMINISTER: Intermittent/Continuous: Give intermittent infusion over at least 1 h and continuous infusion at a rate required to infuse the daily dose in 24 h. With high doses, IV penicillin G should be administered slowly to avoid electrolyte imbalance from potassium or sodium content. Physician will often prescribe specific flow rate.  

INCOMPATIBILITIES Solution/additive: Dextran 40, fat emulsion, aminophylline, amphotericin B, cephalothin, chlorpromazine, dopamine, hydroxyzine, metaraminol, tetracyclines, pentobarbital, prochlorperazine, promazine, sodium bicarbonate, thiopental, metoclopramide.

Adverse Effects (1%)

Body as a Whole: Coughing, sneezing, feeling of uneasiness; systemic anaphylaxis, fever, widespread increase in capillary permeability and vasodilation with resulting edema (mouth, tongue, pharynx, larynx), laryngospasm, malaise, serum sickness (fever, malaise, pruritus, urticaria, lymphadenopathy, arthralgia, angioedema of face and extremities, neuritis prostration, eosinophilia), SLE-like syndrome, Injection site reactions (pain, inflammation, abscess, phlebitis), superinfections (especially with Candida and gram-negative bacteria), neuromuscular irritability (twitching, lethargy, confusion, stupor, hyperreflexia, multifocal myoclonus, localized or generalized seizures, coma). CV: Hypotension, circulatory collapse, cardiac arrhythmias, cardiac arrest. GI: Vomiting, diarrhea, severe abdominal cramps, nausea, epigastric distress, diarrhea, flatulence, dark discoloration of tongue, sore mouth or tongue. Urogenital: Interstitial nephritis, Loeffler's syndrome, vasculitis. Hematologic: Hemolytic anemia, thrombocytopenia. Metabolic: Hyperkalemia (penicillin G potassium); hypokalemia, alkalosis, hypernatremia, CHF (penicillin G sodium). Respiratory: Bronchospasm, asthma. Skin: Itchy palms or axilla, pruritus, urticaria, flushed skin, delayed skin rashes ranging from urticaria to exfoliative dermatitis, Stevens-Johnson syndrome, fixed-drug eruptions, contact dermatitis.

Diagnostic Test Interference

Blood grouping and compatibility tests: possible interference associated with penicillin doses greater than 20 million units daily. Urine glucose: massive doses of penicillin may cause false-positive test results with Benedict's solution and possibly Clinitest but not with glucose oxidase methods (e.g., Clinistix, Diastix, TesTape). Urine protein: massive doses of penicillin can produce false-positive results when turbidity measures are used (e.g., acetic acid and heat, sulfo-salicylic acid); Ames reagent reportedly not affected. Urinary PSP excretion tests: false decrease in urinary excretion of PSP. Urinary steroids: large IV doses of penicillin may interfere with accurate measurement of urinary 17-OHCS (Glenn-Nelson technique not affected).


Drug: Probenecid decreases renal elimination; penicillin G may decrease efficacy of oral contraceptives; colestipol decreases penicillin absorption; potassium-sparing diuretics may cause hyperkalemia with penicillin G potassium. Food: Food increases breakdown in stomach.


Absorption: 15–30% of PO dose absorbed; very acid labile. Peak: 30–60 min PO; 15–30 min IM. Distribution: Widely distributed; good CSF concentrations with inflamed meninges; crosses placenta; distributed in breast milk. Metabolism: 16–30% metabolized. Elimination: 60% excreted in urine within 6 h. Half-Life: 0.4–0.9 h.

Nursing Implications

Assessment & Drug Effects

Patient & Family Education

Common adverse effects in italic, life-threatening effects underlined; generic names in bold; classifications in SMALL CAPS; Canadian drug name; Prototype drug