Cefotetan

2.1 General Dosing Considerations

Rash

There are suggestions, yet to be proven, that the risk of severe, potentially life threatening rash may be increased by (1) coadministration of lamotrigine with valproate, (2) exceeding the recommended initial dose of lamotrigine, or (3) exceeding the recommended dose escalation for lamotrigine. However, cases have occurred in the absence of these factors [see Boxed Warning]. Therefore, it is important that the dosing recommendations be followed closely.

The risk of nonserious rash may be increased when the recommended initial dose and/or the rate of dose escalation for lamotrigine is exceeded and in patients with a history of allergy or rash to other AEDs.

It is recommended that lamotrigine not be restarted in patients who discontinued due to rash associated with prior treatment with lamotrigine, unless the potential benefits clearly outweigh the risks. If the decision is made to restart a patient who has discontinued lamotrigine, the need to restart with the initial dosing recommendations should be assessed. The greater the interval of time since the previous dose, the greater consideration should be given to restarting with the initial dosing recommendations. If a patient has discontinued lamotrigine for a period of more than 5 half-lives, it is recommended that initial dosing recommendations and guidelines be followed. The half-life of lamotrigine is affected by other concomitant medications [see Clinical Pharmacology (12.3)].

Lamotrigine Added to Drugs Known to Induce or Inhibit Glucuronidation: Because lamotrigine is metabolized predominantly by glucuronic acid conjugation, drugs that are known to induce or inhibit glucuronidation may affect the apparent clearance of lamotrigine. Drugs that induce glucuronidation include carbamazepine, phenytoin, phenobarbital, primidone, rifampin, estrogen-containing oral contraceptives, and the protease inhibitors lopinavir/ritonavir and atazanavir/ritonavir. Valproate inhibits glucuronidation. For dosing considerations for lamotrigine in patients on estrogen-containing contraceptives and atazanavir/ritonavir, see below and Table 13. For dosing considerations for lamotrigine in patients on other drugs known to induce or inhibit glucuronidation, see Tables 1, 2, 5, 6, and 13.

Target Plasma Levels for Patients with Epilepsy or Bipolar Disorder: A therapeutic plasma concentration range has not been established for lamotrigine. Dosing of lamotrigine should be based on therapeutic response [see Clinical Pharmacology (12.3)].

Women Taking Estrogen-Containing Oral Contraceptives: Starting Lamotrigine in  Women Taking Estrogen-Containing Oral Contraceptives: Although estrogen-containing  oral contraceptives have been shown to increase the clearance of lamotrigine [see Clinical  Pharmacology (12.3)], no adjustments to the recommended dose-escalation guidelines for  lamotrigine should be necessary solely based on the use of estrogen-containing oral contraceptives. Therefore, dose escalation should follow the recommended guidelines for initiating adjunctive therapy with lamotrigine based on the concomitant AED or other concomitant medications (see Tables 1, 5 and 7). See below for adjustments to maintenance doses of lamotrigine in women taking estrogen-containing oral contraceptives.

     

Adjustments to the Maintenance Dose of Lamotrigine in Women Taking Estrogen-Containing Oral Contraceptives:

(1) Taking Estrogen-Containing Oral Contraceptives: In women not taking carbamazepine, phenytoin, phenobarbital, primidone, or other drugs such as rifampin and the protease inhibitors lopinavir/ritonavir and atazanavir/ritonavir that induce lamotrigine glucuronidation [see Drug Interactions (7), Clinical Pharmacology (12.3)], the maintenance dose of lamotrigine will in most cases need to be increased, by as much as 2-fold over the recommended target maintenance dose, to maintain a consistent lamotrigine plasma level.

(2) Starting Estrogen-Containing Oral Contraceptives: In women taking a stable dose of lamotrigine and not taking carbamazepine, phenytoin, phenobarbital, primidone, or other drugs such as rifampin and the protease inhibitors lopinavir/ritonavir and atazanavir/ritonavir that induce lamotrigine glucuronidation [see Drug Interactions (7), Clinical Pharmacology (12.3)], the maintenance dose will in most cases need to be increased by as much as 2-fold to maintain a consistent lamotrigine plasma level. The dose  increases should begin at the same time that the oral contraceptive is introduced and continue, based on clinical response, no more rapidly than 50 to 100 mg/day every week. Dose increases should not exceed the recommended rate (see Tables 1 and 5) unless lamotrigine plasma levels or clinical response support larger increases. Gradual transient increases in lamotrigine plasma levels may occur during the week of inactive hormonal preparation (pill-free week), and these increases will be greater if dose increases are made in the days before or during the week of inactive hormonal preparation. Increased lamotrigine plasma levels could result in additional adverse reactions, such as dizziness, ataxia, and diplopia. If adverse reactions attributable to lamotrigine consistently occur during the pill-free week, dose adjustments to the overall maintenance dose may be necessary. Dose adjustments limited to the pill-free week are not recommended. For women taking lamotrigine in addition to carbamazepine, phenytoin, phenobarbital, primidone, or other drugs such as rifampin and the protease inhibitors lopinavir/ritonavir and atazanavir/ritonavir that induce lamotrigine glucuronidation [see Drug Interactions (7), Clinical Pharmacology (12.3)], no adjustment to the dose of lamotrigine should be necessary.

(3) Stopping Estrogen-Containing Oral Contraceptives: In women not taking carbamazepine, phenytoin, phenobarbital, primidone, or other drugs such as rifampin and the protease inhibitors lopinavir/ritonavir and atazanavir/ritonavir that induce lamotrigine glucuronidation [see Drug Interactions (7), Clinical Pharmacology (12.3)], the maintenance dose of lamotrigine will in most cases need to be decreased by as much as 50% in order to maintain a consistent lamotrigine plasma level. The decrease in dose of lamotrigine should not exceed 25% of the total daily dose per week over a 2-week period, unless clinical response or lamotrigine plasma levels indicate otherwise [see Clinical Pharmacology (12.3)]. In women taking lamotrigine in addition to carbamazepine, phenytoin, phenobarbital, primidone, or other drugs such as rifampin and the protease inhibitors lopinavir/ritonavir and atazanavir/ritonavir that induce lamotrigine glucuronidation [see Drug Interactions (7), Clinical Pharmacology (12.3)], no adjustment to the dose of lamotrigine should be necessary.

Women and Other Hormonal Contraceptive Preparations or Hormone Replacement Therapy The effect of other hormonal contraceptive preparations or hormone replacement therapy on the pharmacokinetics of lamotrigine has not been systematically evaluated. It has been reported that ethinylestradiol, not progestogens, increased the clearance of lamotrigine up to 2-fold, and the progestin-only pills had no effect on lamotrigine plasma levels. Therefore, adjustments to the dosage of lamotrigine in the presence of progestogens alone will likely not be needed.

Patients Taking Atazanavir/Ritonavir While atazanavir/ritonavir does reduce the lamotrigine plasma concentration, no adjustments to the recommended dose-escalation guidelines for lamotrigine should be necessary solely based on the use of atazanavir/ritonavir. Dose escalation should follow the recommended guidelines for initiating adjunctive therapy with lamotrigine based on concomitant AED or other concomitant medications (see Tables 1, 2, and 5). In patients already taking maintenance doses of lamotrigine and not taking glucuronidation inducers, the dose of lamotrigine may need to be increased if atazanavir/ritonavir is added, or decreased if atazanavir/ritonavir is discontinued [Clinical Pharmacology (12.3)].

Patients with Hepatic Impairment Experience in patients with hepatic impairment is limited. Based on a clinical pharmacology study in 24 subjects with mild, moderate, and severe liver impairment [see Use in Specific Populations (8.6), Clinical Pharmacology (12.3)], the following general recommendations can be made. No dosage adjustment is needed in patients with mild liver impairment. Initial, escalation, and maintenance doses should generally be reduced by approximately 25% in patients with moderate and severe liver impairment without ascites and 50% in patients with severe liver impairment with ascites. Escalation and maintenance doses may be adjusted according to clinical response.

Patients with Renal Impairment Initial doses of lamotrigine should be based on patients' concomitant medications (see Tables 1-3 and 5); reduced maintenance doses may be effective for patients with significant renal impairment [see Use in Specific Populations (8.7), Clinical Pharmacology (12.3)]. Few patients with severe renal impairment have been evaluated during chronic treatment with lamotrigine. Because there is inadequate experience in this population, lamotrigine should be used with caution in these patients.

Discontinuation Strategy Epilepsy: For patients receiving lamotrigine in combination with other AEDs, a re-evaluation of all AEDs in the regimen should be considered if a change in seizure control or an appearance or worsening of adverse reactions is observed.

If a decision is made to discontinue therapy with lamotrigine, a step-wise reduction of dose over at least 2 weeks (approximately 50% per week) is recommended unless safety concerns require a more rapid withdrawal [see Warnings and Precautions (5.8)].

Discontinuing carbamazepine, phenytoin, phenobarbital, primidone, or other drugs such as rifampin and the protease inhibitors lopinavir/ritonavir and atazanavir/ritonavir that induce lamotrigine glucuronidation should prolong the half-life of lamotrigine; discontinuing valproate should shorten the half-life of lamotrigine.

Bipolar Disorder: In the controlled clinical trials, there was no increase in the incidence, type, or severity of adverse reactions following abrupt termination of lamotrigine. In the clinical development program in adults with bipolar disorder, 2 patients experienced seizures shortly after abrupt withdrawal of lamotrigine. Discontinuation of lamotrigine should involve a step-wise reduction of dose over at least 2 weeks (approximately 50% per week) unless safety concerns require a more rapid withdrawal [see Warnings and Precautions (5.8)].

2.2 Epilepsy – Adjunctive Therapy

This section provides specific dosing recommendations for patients older than 12 years and patients aged 2 to 12 years. Within each of these age-groups, specific dosing recommendations are provided depending upon concomitant AED or other concomitant medications (see Table 1 for patients older than 12 years and Table 2 for patients aged 2 to 12 years). A weight-based dosing guide for patients aged 2 to 12 years of age on concomitant valproate is provided in Table 3.

Patients Older Than 12 Years Recommended dosing guidelines are summarized in Table 1.

Table 1. Escalation Regimen for Lamotrigine in Patients Older than 12 Years with Epilepsy

a Valproate has been shown to inhibit glucuronidation and decrease the apparent clearance of lamotrigine [see Drug Interactions (7), Clinical Pharmacology (12.3)].

b Drugs that induce lamotrigine glucuronidation and increase clearance, other than the specified antiepileptic drugs, include estrogen containing oral contraceptives, rifampin, and the protease inhibitors lopinavir/ritonavir and atazanavir/ritonavir can be found in General Dosing Considerations [see Dosage and Administration (2.1)]. Patients on rifampin and the protease inhibitor lopinavir/ritonavir should follow the same dosing titration/maintenance regimen used with antiepileptic drugs that induce glucuronidation and increase clearance [see Dosage and Administration (2.1), Drug Interactions (7), and Clinical Pharmacology (12.3)].

 
In Patients
TAKING
Valproate a
In Patients NOT TAKING
Carbamazepine,
Phenytoin,
Phenobarbital,
Primidone,b or
Valproate a
In Patients
TAKING
Carbamazepine,
Phenytoin,
Phenobarbital, or
Primidone b and NOT
TAKING Valproate a
Weeks 1 and 2
25 mg
every other day
25 mg every day
50 mg/day
Weeks 3 and 4
25 mg every day
50 mg/day
100 mg/day (in 2 divided doses)
Weeks 5 
onwards to 
maintenance
Increase by 25 to
50 mg/day every 1
to 2 weeks
Increase by 50 mg/day
every 1 to 2 weeks
Increase by
100 mg/day every 1
to 2 weeks
Usual 
Maintenance
 dose
100 to 200 mg/day with
valproate alone
100 to 400 mg/day with
valproate and other drugs that
induce glucuronidation
(in 1 or 2 divided doses)
225 to 375 mg/day
(in 2 divided doses)
300 to 500 mg/day
(in 2 divided doses)

Patients Aged 2 to 12 Years Recommended dosing guidelines are summarized in Table 2.

Lower starting doses and slower dose escalations than those used in clinical trials are recommended because of the suggestion that the risk of rash may be decreased by lower starting doses and slower dose escalations. Therefore, maintenance doses will take longer to reach in clinical practice than in clinical trials. It may take several weeks to months to achieve an individualized maintenance dose. Maintenance doses in patients weighing less than 30 kg, regardless of age or concomitant AED, may need to be increased as much as 50%, based on clinical response.

Table 2. Escalation Regimen for Lamotrigine in Patients Aged 2 to 12 Years with Epilepsy

Note: Only whole tablets should be used for dosing.

aValproate has been shown to inhibit glucuronidation and decrease the apparent clearance of lamotrigine [see Drug Interactions (7), Clinical Pharmacology (12.3)].

bDrugs that induce lamotrigine glucuronidation and increase clearance other than the specified antiepileptic drugs, include estrogen-containing oral contraceptives, rifampin, and the protease inhibitors lopinavir/ritonavir and atazanavir/ritonavir. Dosing recommendations for oral contraceptives and the protease inhibitor atazanavir/ritonavir can be found in General Dosing Considerations [see Dosage and Administration (2.1)]. Patients on rifampin, and the protease inhibitor lopinavir/ritonavir should follow the same dosing titration/maintenance regimen used with antiepileptic drugs that induce glucuronidation and increase clearance [see Dosage and Administration (2.1), Drug Interactions (7), and Clinical Pharmacology (12.3)].

In Patients TAKING
Valproate a
In Patients NOT 
TAKING 
Carbamazepine, 
Phenytoin, 
Phenobarbital,   
Primidone, b  or
 Valproate a
In Patients TAKING
 Carbamazepine, 
Phenytoin, 
Phenobarbital, or  
Primidone b and NOT 
TAKING Valproate a
Weeks 1 and 2
0.15 mg/kg/day
 in 1 or 2 divided doses, rounded
 down to the nearest whole tablet
 (see Table 3 for weight based 
dosing guide)
0.3 mg/kg/day 
in 1 or 2 divided doses, 
rounded down to the nearest
 whole tablet
0.6 mg/kg/day 
in 2 divided doses,
 rounded down to the 
nearest whole tablet
Weeks 3 and 4
0.3 mg/kg/day 
in 1 or 2 divided doses, rounded 
down to the nearest whole tablet
 (see Table 3 for weight based 
dosing guide)
0.6 mg/kg/day  in 2 divided doses, 
rounded down to the nearest
 whole tablet
1.2 mg/kg/day
  in 2 divided doses,
 rounded down to the 
nearest whole tablet
Weeks 5 
onwards to 
maintenance
The dose should be increased 
every 1 to 2 weeks as follows: 
calculate 0.3 mg/kg/day, round 
this amount down to the nearest 
whole tablet, and add this 
amount to the previously 
administered daily dose
The dose should be 
increased every 1 to 2 
weeks as follows: calculate 
0.6 mg/kg/day, round this 
amount down to the nearest
 whole tablet, and add this 
amount to the previously 
administered daily dose
The dose should be 
increased every 1 to 2
 weeks as follows: 
calculate 1.2 mg/kg/day,
 round this amount 
down to the nearest 
whole tablet, and add 
this amount to the 
previously administered
 daily dose
Usual Maintenance 
Dose
1 to 5 mg/kg/day
(maximum 200 mg/day
 in 1 or 2 divided doses). 
1 to 3 mg/kg/day 
with valproate alone
4.5 to 7.5 mg/kg/day
 (maximum 300 mg/day
 in 2 divided doses)
5 to 15 mg/kg/day
 (maximum 400 mg/day
 in 2 divided doses)
Maintenance dose in 
patients less than 30 kg
May need to be 
increased by as much as 50%, 
based on clinical response
May need to be increased
 by as much as 50%, based 
on clinical response
May need to be 
increased by as much as
 50%, based on clinical 
response
Table 3. The Initial Weight-Based Dosing Guide for Patients Aged 2 to 12 Years Taking Valproate (Weeks 1 to 4) with Epilepsy If the patient’s weight is
Give this daily dose, using the most appropriate
combination of Lamotrigine 2-mg and 5-mg tablets
Greater than
And less than
Weeks 1 and 2
Weeks 3 and 4
6.7 kg
14 kg
2 mg every other day
2 mg every day
14.1 kg
27 kg
2 mg every day
4 mg every day
27.1 kg
34 kg
4 mg every day
8 mg every day
34.1 kg
40 kg
5 mg every day
10 mg every day

Usual Adjunctive Maintenance Dose for Epilepsy: The usual maintenance doses identified in Tables 1 and 2 are derived from dosing regimens employed in the placebo-controlled adjunctive trials in which the efficacy of lamotrigine was established. In patients receiving multidrug regimens employing carbamazepine, phenytoin, phenobarbital, or primidone without valproate, maintenance doses of adjunctive lamotrigine as high as 700 mg/day have been used. In patients receiving valproate alone, maintenance doses of adjunctive lamotrigine as high as 200 mg/day have been used. The advantage of using doses above those recommended in Tables 1-4 has not been established in controlled trials.

2.3 Epilepsy – Conversion from Adjunctive Therapy to Monotherapy

The goal of the transition regimen is to attempt to maintain seizure control while mitigating the risk of serious rash associated with the rapid titration of lamotrigine.

The recommended maintenance dose of lamotrigine as monotherapy is 500 mg/day given in 2 divided doses.

To avoid an increased risk of rash, the recommended initial dose and subsequent dose escalations for lamotrigine should not be exceeded [see Boxed Warning].

Conversion from Adjunctive Therapy with Carbamazepine, Phenytoin, Phenobarbital, or Primidone to Monotherapy with Lamotrigine: After achieving a dose of 500 mg/day of lamotrigine using the guidelines in Table 1, the concomitant enzyme-inducing AED should be withdrawn by 20% decrements each week over a 4-week period. The regimen for the withdrawal of the concomitant AED is based on experience gained in the controlled monotherapy clinical trial.

Conversion from Adjunctive Therapy with Valproate to Monotherapy with Lamotrigine:  The conversion regimen involves the 4 steps outlined in Table 4.

Table 4. Conversion from Adjunctive Therapy with Valproate to Monotherapy with Lamotrigine in Patients Aged 16 Years and Older with Epilepsy
Lamotrigine
Valproate
Step 1
Achieve a dose of 200 mg/day according 
to guidelines in Table 1 (if not already on 
200 mg/day).
Maintain established stable dose.
Step 2
Maintain at 200 mg/day.
Decrease dose by decrements
 no greater than 500 mg/day/week to  500 mg/day and then maintain for 1 week.
Step 3
Increase to 300 mg/day and maintain for
 1 week.
Simultaneously decrease to 250
 mg/day and maintain for 1 week.
Step 4
Increase by 100 mg/day every week to
 achieve maintenance dose of 500 mg/day.
Discontinue.

Conversion from Adjunctive Therapy with Antiepileptic Drugs other than Carbamazepine, Phenytoin, Phenobarbital, Primidone, or Valproate to Monotherapy with Lamotrigine: No specific dosing guidelines can be provided for conversion to monotherapy with lamotrigine with AEDs other than carbamazepine, phenytoin, phenobarbital, primidone, or valproate.

2.4 Bipolar Disorder

The goal of maintenance treatment with lamotrigine is to delay the time to occurrence of mood episodes (depression, mania, hypomania, mixed episodes) in patients treated for acute mood episodes with standard therapy. [see Indications and Usage (1) ].

Patients taking lamotrigine for more than 16 weeks should be periodically reassessed to determine the need for maintenance treatment.

Adults

The target dose of lamotrigine is 200 mg/day (100 mg/day in patients taking valproate, which decreases the apparent clearance of lamotrigine, and 400 mg/day in patients not taking valproate and taking either carbamazepine, phenytoin, phenobarbital, primidone, or other drugs such as rifampin and the protease inhibitors lopinavir/ritonavir that increase the apparent clearance of lamotrigine). In the clinical trials, doses up to 400 mg/day as monotherapy were evaluated; however, no additional benefit was seen at 400 mg/day compared with 200 mg/day [see Clinical Studies (14.2)]. Accordingly, doses above 200 mg/day are not recommended. Treatment with lamotrigine is introduced, based on concurrent medications, according to the regimen outlined in Table 5. If other psychotropic medications are withdrawn following stabilization, the dose of lamotrigine should be adjusted. In patients discontinuing valproate, the dose of lamotrigine should be doubled over a 2-week period in equal weekly increments (see Table 6).

In patients discontinuing carbamazepine, phenytoin, phenobarbital, primidone, or other drugs such as rifampin and the protease inhibitors lopinavir/ritonavir and atazanavir/ritonavir that induce lamotrigine glucuronidation, the dose of lamotrigine should remain constant for the first week and then should be decreased by half over a 2-week period in equal weekly decrements (see Table 6). The dose of lamotrigine may then be further adjusted to the target dose (200 mg) as clinically indicated.

If other drugs are subsequently introduced, the dose of lamotrigine may need to be adjusted. In particular, the introduction of valproate requires reduction in the dose of lamotrigine [see Drug Interactions (7), Clinical Pharmacology (12.3)]. 

     To avoid an increased risk of rash, the recommended initial dose and subsequent dose escalations of lamotrigine should not be exceeded [see Boxed Warning]. 

Table 5. Escalation Regimen for Lamotrigine in Adults with Bipolar Disorder

aValproate has been shown to inhibit glucuronidation and decrease the apparent clearance of lamotrigine [see Drug Interactions (7), Clinical Pharmacology (12.3)].

bDrugs that induce lamotrigine glucuronidation and increase clearance, other than the specified antiepileptic drugs, include estrogen-containing oral contraceptives, rifampin, and the protease inhibitors lopinavir/ritonavir and atazanavir/ritonavir. Dosing recommendations for oral contraceptives can be found in General Dosing Considerations [see Dosage and Administration (2.1)]. Patients on rifampin and the protease inhibitor lopinavir/ritonavir should follow the same dosing titration/maintenance regimen used with antiepileptic drugs that induce glucuronidation and increase clearance [see Dosage and Administration (2.1), Drug Interactions (7), and Clinical Pharmacology (12.3)].

In Patients TAKING 
Valproate a
In Patients NOT 
TAKING 
Carbamazepine, 
Phenytoin, 
Phenobarbital, 
Primidone, b or 
Valproate a
In Patients TAKING
 Carbamazepine, 
Phenytoin, 
Phenobarbital, or 
Primidone b and NOT 
TAKING Valproate a
Weeks 1 and 2
25 mg every other day
25 mg daily
50 mg daily
Weeks 3 and 4
25 mg daily
50 mg daily
100 mg daily, in 
divided doses
Week 5
50 mg daily
100 mg daily
200 mg daily, in 
divided doses
Week 6
100 mg daily
200 mg daily
300 mg daily, in
 divided doses
Week 7
100 mg daily
200 mg daily
up to 400 mg daily,
 in divided doses

Table 6. Dosage Adjustments to Lamotrigine in Adults with Bipolar Disorder Following Discontinuation of Psychotropic Medications

aValproate has been shown to inhibit glucuronidation and decrease the apparent clearance of lamotrigine [see Drug Interactions (7), Clinical Pharmacology (12.3)].

bDrugs that induce lamotrigine glucuronidation and increase clearance, other than the specified antiepileptic drugs include estrogen-containing oral contraceptives, rifampin, and the protease inhibitors lopinavir/ritonavir and atazanavir/ritonavir. Dosing recommendations for oral contraceptives and the protease inhibitor atazanavir/ritonavir can be found in General Dosing Considerations [see Dosage and Administration (2.1)]. Patients on rifampin and the protease inhibitor lopinavir/ritonavir should follow the same dosing titration/maintenance regimen used with antiepileptic drugs that induce glucuronidation and increase clearance [see Dosage and Administration (2.1), Drug Interactions (7), and Clinical Pharmacology (12.3)].

Discontinuation of
Psychotropic Drugs
(excluding Valproate a, Carbamazepine,
Phenytoin, Phenobarbital,
Primidoneb)
After Discontinuation
of Valproate a
After Discontinuation of
Carbamazepine,
 Phenytoin,
Phenobarbital, or 
Primidone b


Current dose of
Lamotrigine Tablets (mg/day)
100
Current dose of
Lamotrigine Tablets (mg/day)
400
Week 1
Maintain current dose of
lamotrigine tablets
150
400
Week 2
Maintain current dose of
lamotrigine tablets
200
300
Week 3 onward
Maintain current dose of
lamotrigine tablets
200
200

Treatment

The usual adult dosage is 1 or 2 grams of Cefotetan for Injection, USP administered intravenously every 12 hours for 5 to 10 days.  Proper dosage and route of administration should be determined by the condition of the patient, severity of the infection, and susceptibility of the causative organism.

                 General Guidelines for Dosage of Cefotetan for Injection, USP

Type of Infection

Daily Dose

Frequency and Route

Urinary Tract

1 to 4 grams

500 mg every 12 hours IV

1 or 2 g every 24 hours IV

1 or 2 g every 12 hours IV

Skin & Skin Structure

   Mild - Moderatea

    Severe

2 grams

2 g every 24 hours IV

1 g every 12 hours IV

 4 grams
 2 g every 12 hours IV

Other Sites

2 to 4 grams

1 or 2 g every 12 hours IV

Severe

4 grams

2 g every 12 hours IV

Life-Threatening

6 gramsb

3 g every 12 hours IV

a Klebsiella pneumoniae skin and skin structure infections should be treated with 1 or 2 grams every 12 hours IV.

bMaximum daily dosage should not exceed 6 grams.

If Chlamydia trachomatis is a suspected pathogen in gynecologic infections, appropriate antichlamydial coverage should be added, since cefotetan has no activity against this organism.

Prophylaxis

To prevent postoperative infection in clean contaminated or potentially contaminated surgery in adults, the recommended dosage is 1 or 2 g of Cefotetan for Injection, USP administered once, intravenously, 30 to 60 minutes prior to surgery.  In patients undergoing cesarean section, the dose should be administered as soon as the umbilical cord is clamped.

Impaired Renal Function

When renal function is impaired, a reduced dosage schedule must be employed.  The following dosage guidelines may be used.

DOSAGE GUIDELINES FOR PATIENTS WITH IMPAIRED RENAL FUNCTION

Creatinine Clearance

mL/min

Dose

Frequency

> 30

Usual Recommended Dosage*

Every 12 hours

10 to 30

Usual Recommended Dosage*

Every 24 hours

< 10

Usual Recommended Dosage*

Every 48 hours

* Dose determined by the type and severity of infection, and susceptibility of the causative organism.

Alternatively, the dosing interval may remain constant at 12 hour intervals, but the dose reduced to one-half the usual recommended dose for patients with a creatinine clearance of 10 to 30 mL/min, and one-quarter the usual recommended dose for patients with a creatinine clearance of less than 10 mL/min.

When only serum creatinine levels are available, creatinine clearance may be calculated from the following formula.  The serum creatinine level should represent a steady state of renal function.

Males:                 Weight (kg) x (140 - age)                

                      72 x serum creatinine (mg/100 mL)

Females:   0.85 x value for males

 

Cefotetan is dialyzable and it is recommended that for patients undergoing intermittent hemodialysis, one-quarter of the usual recommended dose be given every 24 hours on days between dialysis and one-half the usual recommended dose on the day of dialysis.

Preparation of Solution for Pharmacy Bulk Package for Intravenous Use - NOT FOR DIRECT INFUSION

 

RECONSTITUTED STOCK SOLUTION MUST BE TRANSFERRED AND FURTHER DILUTED FOR IV INFUSION.

Reconstitute with Sterile Water for Injection; 5% Dextrose Injection; or 0.9% Sodium Chloride Injection.  Shake to dissolve and let stand until clear (see DIRECTIONS FOR PROPER USE OF PHARMACY BULK PACKAGE).

Pharmacy

Bulk

Package bottle

Amount of

Diluent to be

Added (mL)

Approximate Withdrawable

Vol (mL)

Approximate

Average Concentration(mg/mL)

10 gram

Pharmacy Bulk

50

55

180

10 gram

Pharmacy Bulk

100

105

95

Intravenous Administration

The intravenous route is preferable for patients with bacteremia, bacterial septicemia, or other severe or life-threatening infections, or for patients who may be poor risks because of lowered resistance resulting from such debilitating conditions as malnutrition, trauma, surgery, diabetes, heart failure, or malignancy, particularly if shock is present or impending.

For intermittent intravenous administration: Using an infusion system, a solution containing 1 gram or 2 grams cefotetan may be administered over 20 to 60 minutes through the tubing system by which the patient may be receiving other intravenous solutions.  Butterfly® or scalp vein-type needles are preferred for this type of infusion.  However, during infusion of the solution containing Cefotetan for Injection, USP, it is advisable to discontinue temporarily the administration of other solutions at the same site.

Note: Solutions of Cefotetan for Injection, USP must not be admixed with solutions containing aminoglycosides.  If Cefotetan for Injection, USP and aminoglycosides are to be administered to the same patient, they must be administered separately and not as a mixed injection.  DO NOT ADD SUPLEMENTATARY MEDICATION.

Treatment

The usual adult dosage is 1 or 2 grams of Cefotetan for Injection, USP administered intravenously every 12 hours for 5 to 10 days.  Proper dosage and route of administration should be determined by the condition of the patient, severity of the infection, and susceptibility of the causative organism.

                 General Guidelines for Dosage of Cefotetan for Injection, USP

Type of Infection

Daily Dose

Frequency and Route

Urinary Tract

1 to 4 grams

500 mg every 12 hours IV

1 or 2 g every 24 hours IV

1 or 2 g every 12 hours IV

Skin & Skin Structure

   Mild - Moderatea

    Severe

2 grams

2 g every 24 hours IV

1 g every 12 hours IV

 4 grams
 2 g every 12 hours IV

Other Sites

2 to 4 grams

1 or 2 g every 12 hours IV

Severe

4 grams

2 g every 12 hours IV

Life-Threatening

6 gramsb

3 g every 12 hours IV

a Klebsiella pneumoniae skin and skin structure infections should be treated with 1 or 2 grams every 12 hours IV.

bMaximum daily dosage should not exceed 6 grams.

If Chlamydia trachomatis is a suspected pathogen in gynecologic infections, appropriate antichlamydial coverage should be added, since cefotetan has no activity against this organism.

Prophylaxis

To prevent postoperative infection in clean contaminated or potentially contaminated surgery in adults, the recommended dosage is 1 or 2 g of Cefotetan for Injection, USP administered once, intravenously, 30 to 60 minutes prior to surgery.  In patients undergoing cesarean section, the dose should be administered as soon as the umbilical cord is clamped.

Impaired Renal Function

When renal function is impaired, a reduced dosage schedule must be employed.  The following dosage guidelines may be used.

DOSAGE GUIDELINES FOR PATIENTS WITH IMPAIRED RENAL FUNCTION

Creatinine Clearance

mL/min

Dose

Frequency

> 30

Usual Recommended Dosage*

Every 12 hours

10 to 30

Usual Recommended Dosage*

Every 24 hours

< 10

Usual Recommended Dosage*

Every 48 hours

* Dose determined by the type and severity of infection, and susceptibility of the causative organism.

Alternatively, the dosing interval may remain constant at 12 hour intervals, but the dose reduced to one-half the usual recommended dose for patients with a creatinine clearance of 10 to 30 mL/min, and one-quarter the usual recommended dose for patients with a creatinine clearance of less than 10 mL/min.

When only serum creatinine levels are available, creatinine clearance may be calculated from the following formula.  The serum creatinine level should represent a steady state of renal function.

Males:                 Weight (kg) x (140 - age)                

                      72 x serum creatinine (mg/100 mL)

Females:   0.85 x value for males

 

Cefotetan is dialyzable and it is recommended that for patients undergoing intermittent hemodialysis, one-quarter of the usual recommended dose be given every 24 hours on days between dialysis and one-half the usual recommended dose on the day of dialysis.

Preparation of Solution for Pharmacy Bulk Package for Intravenous Use - NOT FOR DIRECT INFUSION

 

RECONSTITUTED STOCK SOLUTION MUST BE TRANSFERRED AND FURTHER DILUTED FOR IV INFUSION.

Reconstitute with Sterile Water for Injection; 5% Dextrose Injection; or 0.9% Sodium Chloride Injection.  Shake to dissolve and let stand until clear (see DIRECTIONS FOR PROPER USE OF PHARMACY BULK PACKAGE).

Pharmacy

Bulk

Package bottle

Amount of

Diluent to be

Added (mL)

Approximate Withdrawable

Vol (mL)

Approximate

Average Concentration(mg/mL)

10 gram

Pharmacy Bulk

50

55

180

10 gram

Pharmacy Bulk

100

105

95

Intravenous Administration

The intravenous route is preferable for patients with bacteremia, bacterial septicemia, or other severe or life-threatening infections, or for patients who may be poor risks because of lowered resistance resulting from such debilitating conditions as malnutrition, trauma, surgery, diabetes, heart failure, or malignancy, particularly if shock is present or impending.

For intermittent intravenous administration: Using an infusion system, a solution containing 1 gram or 2 grams cefotetan may be administered over 20 to 60 minutes through the tubing system by which the patient may be receiving other intravenous solutions.  Butterfly® or scalp vein-type needles are preferred for this type of infusion.  However, during infusion of the solution containing Cefotetan for Injection, USP, it is advisable to discontinue temporarily the administration of other solutions at the same site.

Note: Solutions of Cefotetan for Injection, USP must not be admixed with solutions containing aminoglycosides.  If Cefotetan for Injection, USP and aminoglycosides are to be administered to the same patient, they must be administered separately and not as a mixed injection.  DO NOT ADD SUPLEMENTATARY MEDICATION.