Drug Interaction:
Penicillins include-
Natural-
Penicillin G, Penicillin V
Penicillase -Resistent-
Cloxacillin, Docloxacillin, Methicillin, Nafacillin, Oxacillin
Aminopenicillins-
Amoxicillin, Amoxicillin/Potassium Clavulanate, Ampicillin, Ampicillin/Sulbactum, Becampicillin
Extended spectrum-
Carbenicilin, Mezlocillin, Piperacillin.Tazobactam sodium, Ticarcillin, Ticarcillin/Potassium clavulanate
Refer Penicillin V Potassium
Interacting drugs - summary
Penicillin parentral+
Aminoglycosides parentral
certain penicillins inactivate certain aminoglycosides in vitro. e
Do not mix in the same IV solution. Oral Neomysinreduce the
serum concentration of oral penicillin.
Anticoagulants
Large IV doses of penicillin increase bleeding risks of
anticoagulants by prolonging bleeding time. Conversely,
Nafcillin has been associated with warfarin resistence
Penicillins oral +
Beta-blockers
Ampicillin reduce the bioavailabilty of Atenolol. Case reports
indicated that betablockers potentiate anaphylactic
reactions of penicillin.
Penicillin +
Contraceptives Oral
Efficacy of oral contraceptives reduced. Use of
additional form of contraception during penicillin therapy is
advisable.
Penicillin parentl +
Heparin
Increased risk of bleeding occur, possibly due to additive effect
Allopurinol + Ampicillin
Rate of Ampicillin- induced skin rash appears much higher when
co-administered with allopurinol than with either drug itself.
Chloramphenicol + Penicillins
Synergistic effects develop, but antagonism has been
reported in animal studies
Erythromycin + Penicillins
In vitro tests and clinical studies have demonstrated both
antagonism and synergism with coadministration.
Tetracyclines +Penicillins
Bacteriostatic action of tetracycline derivatives impair the
bactericidal effects of penicillins
Indication:
Treatment of mild to moderately infections due to penicillin-sensitive organisms
Penicillins include- Natural- Penicillin G, Penicillin V Penicillase -Resistent- Cloxacillin, Docloxacillin, Methicillin, Nafacillin, Oxacillin Aminopenicillins- Amoxicillin, Amoxicillin/Potassium Clavulanate, Ampicillin, Ampicillin/Sulbactum, Becampicillin Extended spectrum- Carbenicilin, Mezlocillin, Piperacillin.Tazobactam sodium, Ticarcillin, Ticarcillin/Potassium clavulanate Refer Penicillin V Potassium
Adverse Reaction:
Hypersensitivity-
Adverse reactions ( estimated 1% to 10% )are more likely to occur in individuals with prevoiusly demonstrated hypersenstivity.
In penicillin sensitive individuals with a history of allergy, asthma, or hay fever, the reactions may be immerdiate and severe.
Allergic reactions include, urticaria, angioneurotic edema, laryngnospasm , bronchospasm,
hypertension, vascular collapse, death, maculopapular to exfoliative dermatitis,vesicular eruptions, erythema multiforme (rarely Stevens-Johnson syndrome) reactions resembling serum sickness, laryngeal edema,skin rashes, prostration
Cardiovascular-
Cardiac arrest, cerbrovascular acident, hypotension, papipitatoins, pulmonary embolism,
pulmonary hypertension, syncope, tachycardia, vasovagal reactions, vasodilation
CNS-
Penicilin have caused neurotoxicity ( manifested by convulsions, and seizures, hallucinations, lethargy, neuromuscular hyperirritability ) when given in large doses especially in patients with renal failure. Mental disturbances including agitation , anxiety , combativeness, confusion,depression, hallucination, seizures, weakness and expressed " fear of impending death" have been reported in individuals following single dose therapy for Gonorrhoea with Penicilin G Procaine,which have been a reaction to Procaine.
Reactions have been transcient lasting from 15 to 30 minutes.
GI-
Glossitis, stomatitis, gastritis, sore mouth,or tongue, black hairy tongue, abnormal taste senstaion, nausea, vomiting abdominal pain, or enterocolitis, pseudomembraneous colitis.
Incidence of symptoms particularly diarrhea, is less with amoxicilin and becampicillin than with ampicillin.
GU-
Hematuria, impotence, neurogenic bladder, priapism, proteinuria, renal failure, vaginitis
Hemotologic/lymphatic
Anemia, hemolytic anemia, thrmbocytoipenia, thrombocytopenic purpura, eosinophillia,
leukopenia, granulocytopenia, neutropenia, bone marrow depression, agranulocytosis,a reduction of hemoglobin or hematocrit, prolongation of bleeding time, decrease in WBC and lympocyte counts, increase in lymphocytes, monocytes basophils and platelets
These reactions are reversible on discontinuation of therapy.
Bleeding abnormalities-
Hemorrhagic manifestations associated with abnormalities of coagulation tests such as clotting and prothrombin time occured
Renal-
Interstital nephritis and nephropathy are in frequent and usually associated with high dosesof parentral penicillins( most frequently methicillin). This has also occured with all the penicillins.
Elevations of creatinine or BUN may also occur.
Local-
Pain at injection site , ecchymosis, deep vein thrombosis, hematomas, . Vein irrigation and phlebitis can occur,
Miscellaneous-
Vaginitis, anorexia, hyperthermia, itchy eyes, transcient hepatitis and cholestatic jaundice (rare), sciatic neuritis caused IM injection of penicillin
Lab test abnormalities-
Elevations of AST, ALT, bilirubin and LDH have been noted in patients receiving semisynthtic penicillin (particularly oxacillin and coxacillin). Such reactions are more common in infants.
Elevations of serum alkaline phosphatae and hyponatremia and reduction in serum potassium, albumin, total proteins and uric acid may occur. Evidence indicates glutamic oxaloacetic transaminase (GOT) is released at the site of IM of ampicillin.
Contra-Indications:
Hypersensitivity
Special precautions:
Monitoring- Perform bacteriologic studies to determine causative organism sand their suseptitbility is that appropriate therapy is administered.
Obtain blood cultures,white blood cell and differential counts prior to initiation of therapy and at least weekly during the therapy with penicllinase-resistant penicillins. Measure AST and ALT during therapy to monitor the liver function abnormalities.
Streptococcol infection-
Therapy must be sufficient to eliminate the organism (is minimum in 10 days) otherwise,
sequalae (eg endocarditis, rheumatic fever) ,may occur. Take cultures after treatment to confirm that successful streptococci is eliminated.
Sexually transmitted diseases-
When treating gonoccocol infections in which primary and secondary syphillis are
suspected, perform proper diagnostic procedures, including darkfield examinations and monthly serological tests for at least 4 months. All cases of penicillin treated syphillis should receive clinical and serological examination every 6 months for 2 to 3 years.
Renal function impairment-
Since carbencillin is primarily excreted by the kidney,patients with severe renal impairment
(creatinine clearance < 10ml/mim) will not receive the therapeutic urine levels for carbencillin.In patients with creatinine clearance 10 to 20ml/min, it may be necessary to adjust dosage to prevent accumulation of the drug.
Resistence-
Number of strains of staphyloccoci resistent to penicillase-resistent penicillins has been increasing, wide spread usage of penicillins may result in an increasing number of resistent staphyloccocus strains. Interpret resistence to any penicillase-resistent penicillin as evidence of clinical resistence to all. Cross-resistence with cephalosporin derivatives also occurs frequently.
Pseudomembranous colitis-
Has occured with the use of broad spectrum antibiotics due to overgrowth of clostrida,
therefore it is important to consider its diagnosis in patients who develop diarrhea in association with antibiotic use.
Mild cases may respond with drug discontinuation alone. Manage moderate to severe cases with fluid, electrolyte and protein supplementation.
Procaine sensitivity-
If sensitivity to procaine in Penicillin G procaine is suspected, inject 0.1ml of a 1% to 2% procaine solution intradermally
Parentral administration-
Inadvertant intravascular admnnistration including intra-arterial injection or injection
immediately adjacent to arteries has resulted in severe neuromuscular damage,including transverse myletis with permanent paralysis, gangrene requiring amputation of digits and more proximal portions of extremities, necrosis and sloughing at the surronding injection site.
Such severe effects have occured following injections into the buttock, thigh, and deletoid areas. Promptly consult specialist if any evidence of compromise of the blood supply occurs at proximal to or distal to the site of injection.
Electrolyte imbalance-
Administer aqueous penicillin G IV in high doses (> 10 million units) slowly because of electrolye imbalance from either the potassium or sodium content. When sodium restriction is necessary, (eg cardiac patients)
make periodic electrolyte determinations and monitor the cardiac status.
Superinfection-
Use of antibiotics (especially prolonged or repeated therapy) may result in bacterial or fungal overgrowth of nonsusceptible organisms. Such overgrowth may lead to a secondary infection. Take appropiate measures if this occurs.
Dosages/ Overdosage Etc:
Indications
Oral- Penicillins are generally indicated in the treatment of mild to moderately infections due to penicillin-sensitive organisms. Penicillin V is preferred over Penicillin G for oral use to better absorption.
Penicilase-resistent penicillins- The percentage of staphylococcal isolates resistent to penicillin G outside the hospital is increasing,approximating the high percentage found in hospital.. Therfore, use a penicillanase-resistent penicillin as initial therapy for any suspected staphylococcal infection until culture and sensitivity results are known.
Consider these agents are only effective in the treatment of infections caused by pneumococci, group. A beta-hemolytic streptococci and penicillin G-resistent and penicillin G sensitive staphylococci.
Dosage-
Children- 100,000 to 250,000 units/kg/day in divided doses every 4 hours.
Infants- Over 7 days old- and >2000g- 100,000 units/kg/day in divided doses every 6 hours
(meningitis- 200,000 units)
Over 7 days- and < 2000kg - 75,000 units/kg/day in divided doses every 8 hours
(meningitis- 150,000 units)
Under 7 days old and > 2000g - 50,000 units/kg/day in divided doses every 8 hours
(meningitis- 150,000 units)
Under 7 days old and < 2000g- 50,000 units/kg/day in divided doses every 12 hours
(meningitis- 100,000 units)
Streptococci in groups A,C,G,H,L,and M are very sensitive to penicillin G. Some group D organisms
are sensitive to the high levels obtained with aqueous Penicillin G
Other Information:
For Availability/supplies
Contact -
1.Indian Drug Manufacturers Association (IDMA)
Phone- 022- 24944624/ 24974308
Fax- 022- 24950723
Email- idma@vsnl.com
Website: www.idma-assn.org
2.Bulk Drug Manufacturers Association (India)(BDMA)
Phone - 040-23703910/ 23706718
Fax- 040-23704804
Email- info@bdmai.org
Website: www.info@bdmai.org
Serum Sickness- Immune complex disease ( 347)
Immune -complex disease are characterised by the deposition of antigen-antibody complexes in vascular and glomuerular basement membranes and by the presence of these complexes in the circulation and in other body fluid compartments. The immune complex diseases constitute a ckinicak syndrome which includes glomerulonephritis, arthiritis, skin eruptions, pericardititis, pleuritis, and vasculitis at diverse sites. Once the antigen is completely cleared the complement levels return to normal and gradually the lesions in the target organs subside. Thus the acute serum sickness is a limited disease and progreses only as as the antigen persists in the recipient. Serum sickness- drug induced
1. Aspirin
2. Penicillin
3. Streptomycin
4. Sulfonamides
5. Propylthiouracil
Patient Information:
1. Complete full course of therapy
2. Take on an empty stomach 1 hour before or 2 hours after meals. Absorption of Penicillin V, amoxycillin, becampicillin tablets and amoxycillin/potassium cluvinate is not significantly affected by food.
3. Take each oral dose with a full glass of water, not fruit juice or carbobanated beverage (cloxacillin, penicillin G)
4. Take at even intervals,preferably around the clock.
5. Notify physician, if skin rash, itching, hives, severe diarrhoea, shortness of breath, wheezing, black tongue, sore throat, nausea, vomiting, fever, swollen joints or unusual bleeding or bruising occurs
6. Discard any liquid forms of penicillin after 7 days if stored at room temperature or 14 days if it is refrigerated.
7.Allergies- tell your doctor if you have ever had any unusual or allergic reaction to penicillin or cephalosporins. Also tell your doctor if you are allergic to any other substances, such as foods, presevatives or dyes.
8.Pregnancy - penicillins have been widely used in pregnant woman and have not been shown to cause birth defects or other problems in animal studies.
9.Breast feeding- penicillins pass into breast milk. allergic reactions , diarrhea, fungus infectins and skin rash may occur in nursing babies
10. Children - Many penicillins have been used in children and in effective doses and are not expected to cause different side effects or problems in children than in adults.
11.Elderly- peniciilins have been used in elderly and have not been shown to cause different side effects or problems in older people than in younger adults.
12. Other medicines - Acetoaminophen or Amiodarone or Anabolic steroids or Androgens or Antithyroid agents or Carmustine or Chloroquine or Dantrolene or Daunorubicin or Disulfram or Divalproex or Estrogens or Etretinate or Gold salts or Hydroxychloroquine or
Mercaptopurine or Methotrexate or Methyldopa or Naltrxone or Oral contraceptives or Other anti-infectives by mouth or injection or Phenothiothizines or Plicamycin or Valproic acid - these medicines may increase the chance of liver damage if taken with cloxacillin, dicloxacillin, flucoxacillin, mezlocillin, nafacillin, oxacilin, or pipercillin Amiloride or Benazapril or Captopril or Enalapril or Fosinopril or Lisonopril or Potassium contg medicine or
Quinalapril or Ramipril or Spironloactone or Triamterene - use of these medicines with penicillin G by injection may cause an increase in side effects Anticoagulants or Dipyradamole or Divalaproex or Heparin or Inflammation or pain medicine or
Pentoxyphylline or Plicamycin or Sulfinpyrazone or Valproic acid - use of these medicines with high dose of carbenicillin, pipericillin or ticarcillin may increase the chance of bleeding Chloramphenicol or Erythromycins or Sulfonamides or Tetracycline - use of these medicines with penicillins may prevent the penicillin from working properly Cholestyramine or Colestipol - use of these medicines with oral penicillin G may prevent penicillin G from
working properly Oral contraceptives - use ofampicilin, amoxicillin, or penicillin V with estrogen containg oral contraceptives may prevent oral contraceptives from working properly, increasing the chance of pregnancy Methotrexate - use of methotrexate with penicillins may increase the chance of side effects of methotrexate Probenecid - probenicid causes penicillins to build up in the blood and may increase the chance of side effects
13. Other medical problems - Tell your doctor if you have any other medical problems especially - Allergy such as asthma,eczema, hay fever etc.- patients with a history of general allergies may be more likely to have a severe reaction to penicilin Bleeding problems - patients with a history of bleeding problems may be more likely to bleeding while
receiving carbenicillin, pipericillin or ticarillin Congestive heart failure or High blood pressure - large dose of carbenicilin orticarcillin may make the conditon worse, because these medicines contain large amount of salt. Cystic fibrosis - patients with cystic fibrosis may have an increased chance of fever and skin rash when receiving pipericilin Kidney disease - patients with kidney disease may have an increased chance of side effects Mononucleosis- patients with mononucleosis may have an increased chance of skin rash while receiving
ampicillin, becampicillin, or pivampicilin Stomach or intestinal disease - patients with history of stomach disease or intestinal disease may be more likely to develop colitis while taking penicillins.
11. Missed dose - If you miss a dose of this medicine, take it as soon as possible. however, if it is almost time for the next dose, skip the missed dose. Do not double doses.
12. Storage - Keep out of reach of children. Store away from heat or direct sunlight. Do not store the capsule in bathroom, near the kitchen sink, or in other damp places.
13. Outdated medicines - Do not keep outdated medicine or medicine no longer needed. Be sure that any discarded medicine is out of reach of children.
Pharmacology/ Pharmacokinetics:
Pharmacology:
Penicillins are bactericidal antibiotics that include natural and semisynthetic derivatives. These agents contain the beta-6-aminopenicillinic acid nucleus and have a similar mechanism of action Penicillins inhibit the biosynthesis of cell wall mucopeptide. They are bactericidal against sensitive organisms when adequate concentratins are reached and they are most effective during the stage of active multiplication. Inadequate concentrations may produce only bacteriostatic effects.
Pharmacokinetics:
Oral preparations of Penicillin G are slightly affected by normal gastric acidity(pH 2 to 3.5), however pH less than 2 may partially or totally inactivate it. Absorption of most penicillins is affected by food; these medicines are best taken on an empty stomach, 1 hour before or 2 hours after meals. Peak serum levels occur approximately after i hour after oral use. Penicillins are bound to plasma proteins, primarily albumin, in varying degrees. They diffuse readily into most body tissues and fluids, including kidneys, liver, lungs, heart, skin, synovial fluid, bile, pritoneal fluid etc. Penicillins are excreted largely unchanged in the urine by glomerular filtration and active tubular secretion.
Interaction with Food:
Drug/Food interactions- Absorption of most penicillins is affected by food, these medicatons are best taken on an empty stomach 1 hour before or 2 hours after meals. Penicillin V may be given with meals, however blood levels may be slightly higher when taken on an empty stomach. Amoxicillin, amoxicilin/potassium cluvuanate and becampicillin tablets may be given without regard to meals, Absorption of becampicillin suspension is affected by food.
Pregnancy and lactation:
Pregnancy: No adequate oe well controlled studies in pregnant women. Use only if required. Lactation: Penicillins are excreted in breast milk in low concentration. May cause diarrhoea,, candidiasis or allergic response in the nursing infant.
