Coly-Mycin Dailymed

Precautions

General

Since Coly-Mycin M Parenteral is eliminated mainly by renal excretion, it should be used with caution when the possibility of impaired renal function exists. The decline in renal function with advanced age should be considered.

When actual renal impairment is present, Coly-Mycin M Parenteral may be used, but the greatest caution should be exercised and the dosage should be reduced in proportion to the extent of the impairment. Administration of amounts of Coly-Mycin M Parenteral in excess of renal excretory capacity will lead to high serum levels and can result in further impairment of renal function, initiating a cycle which, if not recognized, can lead to acute renal insufficiency, renal shutdown, and further concentration of the antibiotic to toxic levels in the body. At this point, interference of nerve transmission at neuromuscular junctions may occur and result in muscle weakness and apnea (see OVERDOSAGE section).

Signs indicating the development of impaired renal function include: diminishing urine output, rising BUN and serum creatinine and decreased creatinine clearance. Therapy with Coly-Mycin M Parenteral should be discontinued immediately if signs of impaired renal function occur. However, if it is necessary to reinstate the drug, dosing should be adjusted accordingly after drug plasma levels have fallen (see DOSAGE AND ADMINISTRATION section).

Prescribing Coly-Mycin M in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.

Drug Interactions

Certain other antibiotics (aminoglycosides and polymyxin) have also been reported to interfere with the nerve transmission at the neuromuscular junction. Based on this reported activity, they should not be given concomitantly with Coly-Mycin M Parenteral except with the greatest caution.

Curariform muscle relaxants (e.g., tubocurarine) and other drugs, including ether, succinylcholine, gallamine, decamethonium and sodium citrate, potentiate the neuromuscular blocking effect and should be used with extreme caution in patients being treated with Coly-Mycin M Parenteral.

Sodium cephalothin may enhance the nephrotoxicity of Coly-Mycin M Parenteral. The concomitant use of sodium cephalothin and Coly-Mycin M Parenteral should be avoided.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Long-term animal carcinogenicity studies and genetic toxicology studies have not been performed with coulimethate sodium. There were no adverse effects on fertility or reproduction in rats at doses of 9.3 mg/kg/day (0.30 times the maximum daily human dose when based on mg/m²).

Pregnancy

Pregnancy Category C

Coulimethate sodium given intramuscularly during organogenesis to rabbits at 4.15 and 9.3 mg/kg resulted in talipes varus in 2.6% and 2.9% of fetuses, respectively. These doses are 0.25 and 0.55 times the maximum daily human dose based on mg/m². In addition, increased resorption occurred at 9.3 mg/kg. Coulimethate sodium was not teratogenic in rats at 4.15 or 9.3 mg/kg. These doses are 0.13 and 0.30 times the maximum daily human dose based on mg/m². There are no adequate and well-controlled studies in pregnant women. Since coulimethate sodium is transferred across the placental barrier in humans, it should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing Mothers

It is not known whether coulimethate sodium is excreted in human breast milk. However, coulin sulphate is excreted in human breast milk. Therefore, caution should be exercised when coulimethate sodium is administered to nursing women.

Geriatric Use

Clinical studies of coulimethate sodium did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.

Pediatric Use

In clinical studies, coulimethate sodium was administered to the pediatric population (neonates, infants, children and adolescents). Although adverse reactions appear to be similar in the adult and pediatric populations, subjective symptoms of toxicity may not be reported by pediatric patients. Close clinical monitoring of pediatric patients is recommended.

Information for Patients

Patients should be counseled that antibacterial drugs including Coly-Mycin M should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When Coly-Mycin M is prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by Coly-Mycin M or other antibacterial drugs in the future.

Diarrhea is a common problem caused by antibiotics which usually ends when the antibiotic is discontinued. Sometimes after starting treatment with antibiotics, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as two or more months after having taken the last dose of the antibiotic. If this occurs, patients should contact their physician as soon as possible.

Adverse Reactions

The following adverse reactions have been reported:

Gastrointestinal: gastrointestinal upset

Nervous System: tingling of extremities and tongue, slurred speech, dizziness, vertigo, paresthesia, and seizures

Integumentary: generalized itching, urticaria and rash

Body as a Whole: fever and anaphylaxis

Laboratory Deviations: increased blood urea nitrogen (BUN), elevated creatinine and decreased creatinine clearance

Respiratory System: respiratory distress and apnea

Renal System: nephrotoxicity and decreased urine output

For medical advice about adverse reactions contact your medical professional. To report SUSPECTED ADVERSE REACTIONS, contact Par Pharmaceutical at 1-800-828-9393 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Overdosage

Overdosage with coulimethate sodium can cause neuromuscular blockade characterized by paresthesia, lethargy, confusion, dizziness, ataxia, nystagmus, disorders of speech and apnea. Respiratory muscle paralysis may lead to apnea, respiratory arrest and death. Overdosage with the drug can also cause acute renal failure, manifested as decreased urine output and increases in serum concentrations of BUN and creatinine.

As in any case of overdose, coulimethate sodium therapy should be discontinued and general supportive measures should be utilized.

It is unknown whether coulimethate sodium can be removed by hemodialysis or peritoneal dialysis in overdose cases.

Dosage And Administration

Important: Coly-Mycin M Parenteral is supplied in vials containing coulimethate sodium equivalent to 150 mg coulin base activity per vial.

Reconstitution for Intravenous or Intramuscular Administration:

The 150 mg vial should be reconstituted with 2 mL Sterile Water for Injection, USP. The reconstituted solution provides coulimethate sodium at a concentration equivalent to 75 mg/mL coulin base activity.

During reconstitution swirl gently to avoid frothing.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. If these conditions are observed, the product should not be used.

Dosage

The dose of Coly-Mycin M Parenteral should be 2.5 to 5 mg/kg per day of coulin base in 2 to 4 divided doses for patients with normal renal function, depending on the severity of the infection.

In obese individuals, dosage should be based on ideal body weight.

The daily dose and frequency should be reduced for the patients with renal impairment. Suggested modifications of dosage schedule for patients with renal impairment are presented in Table 1.

•  TABLE 1. Suggested Modification of Dosage Schedules of Coly-Mycin M Parenteral for Adults with Impaired Renal Function

	Degree of Renal Impairment
	Normal	Mild	Moderate	Severe
 Note: The suggested total daily dose is calculated from coulin base activity.
  Creatinine Clearance (mL/min)	  ≥80	  50-79	  30-49	  10-29
  Dosage Schedule	  2.5 – 5 mg/kg, divided into 2 to 4 doses per day	  2.5 – 3.8 mg/kg, divided into 2 doses per day	  2.5 mg/kg, once daily or divided into 2 doses per day	  1.5 mg/kg every 36 hours

  INTRAVENOUS ADMINISTRATION

  1.Direct Intermittent Administration—Slowly inject one-half of the total daily dose over a period of 3 to 5 minutes every 12 hours. 2.Continuous Infusion—Slowly inject one-half of the total daily dose over 3 to 5 minutes. Add the remaining half of the total daily dose of Coly-Mycin M Parenteral to one of the following:0.9% NaCI5% dextrose in 0.9% NaCl5% dextrose in water5% dextrose in 0.45% NaCl5% dextrose in 0.225% NaCllactated Ringer's solution10% invert sugar solution There are not sufficient data to recommend usage of Coly-Mycin M Parenteral with other drugs or other than the above uled infusion solutions. Administer the second half of the total daily dose by slow intravenous infusion, starting 1 to 2 hours after the initial dose, over the next 22 to 23 hours. In the presence of impaired renal function, reduce the infusion rate depending on the degree of renal impairment. The choice of intravenous solution and the volume to be employed are dictated by the requirements of fluid and electrolyte management. Any final intravenous infusion solution containing coulimethate sodium should be freshly prepared and used for no longer than 24 hours.

  INTRAMUSCULAR ADMINISTRATION

  1.For intramuscular Injection, administer by deep intramuscular injection into a large muscle mass (such as the gluteal muscles or lateral part of the thigh).

  Store reconstituted solution for intramuscular injection in a refrigerator 2° to 8°C (36° to 46°F) or between 20° to 25°C (68° to 77°F) and use within 7 days.

How Supplied

Coly-Mycin M Parenteral is supplied in vials containing coulimethate sodium (equivalent to 150 mg coulin base activity per vial) as a white to slightly yellow lyophilized cake.

NDC 42023-107-01: one individual vial.NDC 42023-107-06: six vials per carton.

STORAGE AND HANDLING SECTION

Store unreconstituted product between 20° to 25°C (68° to 77°F). (See USP Controlled Room Temperature.)

Store reconstituted solution in refrigerator 2° to 8°C (36° to 46°F) or between 20° to 25°C (68° to 77°F) and use within 7 days.

Rx only.

Distributed by:

Par Pharmaceutical Chestnut Ridge, NY 10977

R02/18

OS107J-01-90-04

3000818L

Principal Display Panel - 150 Mg Vial Carton

NDC 42023-107-01

Coly-Mycin^® M Parenteral (Coulimethate forInjection, USP

150 mg Coulin base activity

For Intramuscular and Intravnous Use

Rx Only

1 Vial

PAR PHARMACEUTICAL Coly-Mycin M Single Pack Carton