Codeine Sulfate

Selection of patients for treatment with codeine sulfate should be governed by the same principles that apply to the use of similar opioid analgesics. Physicians should individualize treatment in every case, using non-opioid analgesics, opioids on an as needed basis and/or combination products, and chronic opioid therapy in a progressive plan of pain management.

2.1 Individualization of Dosage

As with any opioid drug product, adjust the dosing regimen for each patient individually, taking into account the patient’s prior analgesic treatment experience. In the selection of the initial dose of codeine sulfate, attention should be given to the following:

• the total daily dose, potency and specific characteristics of the opioid the patient has been taking previously;

• the reliability of the relative potency estimate used to calculate the equivalent codeine sulfate dose needed;

• the patient’s degree of opioid tolerance;

• the general condition and medical status of the patient;

• concurrent medications;

• the type and severity of the patient’s pain;

• risk factors for abuse, addiction or diversion, including a prior history of abuse, addiction or diversion.

The following dosing recommendations, therefore, can only be considered suggested approaches to what is actually a series of clinical decisions over time in the management of the pain of each individual patient.

Continual re-evaluation of the patient receiving codeine sulfate is important, with special attention to the maintenance of pain control and the relative incidence of side effects associated with therapy. During chronic therapy, especially for noncancer-related pain, the continued need for the use of opioid analgesics should be re-assessed as appropriate.

During periods of changing analgesic requirements, including initial titration, frequent contact is recommended between physician, other members of the healthcare team, the patient, and the caregiver/family.

2.2 Initiation of Therapy

The usual adult dosage for tablets is 15 mg to 60 mg repeated up to every four hours as needed for pain. The maximum 24 hour dose is 360 mg.

The initial dose should be titrated based upon the individual patient’s response to their initial dose of codeine. This dose can then be adjusted to an acceptable level of analgesia taking into account the improvement in pain intensity and the tolerability of the codeine by the patient.

It should be kept in mind, however, that tolerance to codeine sulfate can develop with continued use and that the incidence of untoward effects is dose-related. Adult doses of codeine higher than 60 mg fail to give commensurate relief of pain and are associated with an appreciably increased incidence of undesirable side effects.

2.3 Cessation of Therapy

When the patient no longer requires therapy with codeine sulfate, doses should be tapered gradually to prevent signs and  symptoms of withdrawal in the physically dependent patient.

Ciprofloxacin should be administered intravenously at dosages described in the appropriate Dosage Guidelines tables.

2.1 Dosage in Adults

The determination of dosage and duration for any particular patient must take into consideration the severity and nature of the infection, the susceptibility of the causative microorganism, the integrity of the patient’s host-defense mechanisms, and the status of renal function.

Table 1: Adult Dosage Guidelines 1   Due to the designated pathogens (see Indications and Usage).
2   Used in conjunction with metronidazole.
3   Begin administration as soon as possible after suspected or confirmed exposure.

Infection1

Dose

Frequency

Usual Duration

Urinary Tract

200 mg to 400 mg

every 12 to every 8 hours

7 to 14 days

Lower Respiratory Tract

400 mg

every 12 to every 8 hours

7 to 14 days

Nosocomial Pneumonia

400 mg

every 8 hours

10 to 14 days

Skin and Skin Structure

400 mg

every 12 to every 8 hours

7 to 14 days

Bone and Joint

400 mg

every 12 to every 8 hours

4 to 8 weeks

Complicated Intra-Abdominal2

400 mg

every 12 hours

7 to 14 days

Acute Sinusitis

400 mg

every 12 hours

10 days

Chronic Bacterial Prostatitis

400 mg

every 12 hours

28 days

Empirical Therapy In Febrile Neutropenic Patients

Ciprofloxacin

400 mg

and

Piperacillin

50 mg/kg

every 8 hours

___________

every 4 hours

7 to 14 days

Inhalational anthrax (post-exposure)3

400 mg

every 12 hours

60 days

Plague3

400 mg

every 12 to 8 hours

14 days

Conversion of Intravenous to Oral Dosing in Adults

Patients whose therapy is started with ciprofloxacin injection may be switched to CIPRO Tablets or Oral Suspension when clinically indicated at the discretion of the physician (Table 2) [see Clinical Pharmacology (12.3)].

Table 2: Equivalent AUC Dosing Regimens

Ciprofloxacin Oral Dosage

Equivalent Ciprofloxacin Injection Dosage

250 mg Tablet every 12 hours

200 mg intravenous every 12 hours

500 mg Tablet every 12 hours

400 mg intravenous every 12 hours

750 mg Tablet every 12 hours

400 mg intravenous every 8 hours

2.2 Dosage in Pediatric Patients

Dosing and initial route of therapy (that is, IV or oral) for cUTI or pyelonephritis should be determined by the severity of the infection.

Table 3: Pediatric Dosage Guidelines 1   The total duration of therapy for cUTI and pyelonephritis in the clinical trial was determined by the physician. The mean duration of treatment was 11 days (range 10 to 21 days).
2   Begin drug administration as soon as possible after suspected or confirmed exposure.
3   Begin drug administration as soon as possible after suspected or confirmed exposure to Y. pestis.

Infection

Route of Administration

Dose (mg/kg)

Frequency

Total Duration

Complicated Urinary Tract or Pyelonephritis (patients from 1 to 17 years of age)1

Intravenous

6 mg/kg to 10 mg/kg (maximum 400 mg per dose; not to be exceeded even in patients weighing >51 kg)

Every 8 hours

10 to 21 days1

Inhalational Anthrax

(Post-Exposure)2

Intravenous

10 mg/kg

(maximum 400 mg per dose)

Every 12 hours

60 days

Plague2,3

Intravenous

10 mg/kg

(maximum 400 mg per dose)

Every 12 to 8 hours

10 to 21 days

2.3 Dosage Modifications in Patients with Renal Impairment

Ciprofloxacin is eliminated primarily by renal excretion; however, the drug is also metabolized and partially cleared through the biliary system of the liver and through the intestine. These alternative pathways of drug elimination appear to compensate for the reduced renal excretion in patients with renal impairment. Nonetheless, some modification of dosage is recommended, particularly for patients with severe renal dysfunction. Dosage guidelines for use in patients with renal impairment are shown in Table 4.

Table 4: Recommended Starting and Maintenance Doses for Adult Patients with Impaired Renal Function

Creatinine Clearance (mL/min)

Dose

> 30

See Usual Dosage

5 to 29

200 to 400 mg every 18 to 24 hours

When only the serum creatinine concentration is known, the following formulas may be used to estimate creatinine clearance:

Men - Creatinine clearance (mL/min) = Weight (kg) x (140 – age)
                                                            72 x serum creatinine (mg/dL)

Women - 0.85 x the value calculated for men.

The serum creatinine should represent a steady state of renal function.

In patients with severe infections and severe renal impairment and hepatic insufficiency, careful monitoring is suggested.

Pediatric patients with moderate to severe renal insufficiency were excluded from the clinical trial of cUTI and pyelonephritis. No information is available on dosing adjustments necessary for pediatric patients with moderate to severe renal insufficiency (that is, creatinine clearance of < 50 mL/min/1.73m2).

2.4 Preparation of Ciprofloxacin for Administration

Vials (Injection Concentrate)

THIS PREPARATION MUST BE DILUTED BEFORE USE. The intravenous dose should be prepared by aseptically withdrawing the concentrate from the vial of Ciprofloxacin Injection. This should be diluted with a suitable intravenous solution to a final concentration of 1 to 2 mg/mL (see COMPATIBILITY AND STABILITY). The resulting solution should be infused over a period of 60 minutes by direct infusion or through a Y-type intravenous infusion set which may already be in place.

If the Y-type or “piggyback” method of administration is used, it is advisable to discontinue temporarily the administration of any other solutions during the infusion of Ciprofloxacin Injection. If the concomitant use of Ciprofloxacin Injection and another drug is necessary each drug should be given separately in accordance with the recommended dosage and route of administration for each drug.

COMPATIBILITY AND STABILITY

Ciprofloxacin Injection 1% (10 mg/mL), when diluted with the following intravenous solutions to concentrations of 0.5 to 2.0 mg/mL, is stable for up to 14 days at refrigerated or room temperature storage.

0.9% Sodium Chloride Injection, USP
5% Dextrose Injection, USP
Sterile Water for Injection
10% Dextrose for Injection
5% Dextrose and 0.225% Sodium Chloride for Injection
5% Dextrose and 0.45% Sodium Chloride for Injection
Lactated Ringer’s for Injection

2.5 Important Administration Instructions

Intravenous Infusion

Ciprofloxacin should be administered to by intravenous infusion over a period of 60 minutes. Slow infusion of a dilute solution into a larger vein will minimize patient discomfort and reduce the risk of venous irritation.

Hydration of Patients Receiving Ciprofloxacin

Adequate hydration of patients receiving ciprofloxacin should be maintained to prevent the formation of highly concentrated urine. Crystalluria has been reported with quinolones [see Warnings and Precautions (5.12), Adverse Reactions (6.1), Nonclinical Toxicology (13.2) and Patient Counseling Information (17)].

Selection of patients for treatment with codeine sulfate should be governed by the same principles that apply to the use of similar opioid analgesics. Physicians should individualize treatment in every case, using non-opioid analgesics, opioids on an as needed basis and/or combination products, and chronic opioid therapy in a progressive plan of pain management.

2.1 Individualization of Dosage

As with any opioid drug product, adjust the dosing regimen for each patient individually, taking into account the patient’s prior analgesic treatment experience. In the selection of the initial dose of codeine sulfate, attention should be given to the following:

The total daily dose, potency and specific characteristics of the opioid the patient has been taking previously; the reliability of the relative potency estimate used to calculate the equivalent codeine sulfate dose needed; the patient’s degree of opioid tolerance; the general condition and medical status of the patient; concurrent medications; the type and severity of the patient’s pain; risk factors for abuse, addiction or diversion, including a prior history of abuse, addiction or diversion.

The following dosing recommendations, therefore, can only be considered suggested approaches to what is actually a series of clinical decisions over time in the management of the pain of each individual patient.

Continual reevaluation of the patient receiving codeine sulfate is important, with special attention to the maintenance of pain control and the relative incidence of side effects associated with therapy. During chronic therapy, especially for noncancer-related pain, the continued need for the use of opioid analgesics should be reassessed as appropriate.

During periods of changing analgesic requirements, including initial titration, frequent contact is recommended between physician, other members of the healthcare team, the patient, and the caregiver/family.

2.2 Initiation of Therapy

The usual adult dosage for tablets is 15 mg to 60 mg repeated up to every four hours as needed for pain. The maximum 24 hour dose is 360 mg.

The initial dose should be titrated based upon the individual patient’s response to their initial dose of codeine. This dose can then be adjusted to an acceptable level of analgesia taking into account the improvement in pain intensity and the tolerability of the codeine by the patient.

It should be kept in mind, however, that tolerance to codeine sulfate can develop with continued use and that the incidence of untoward effects is dose-related. Adult doses of codeine higher than 60 mg fail to give commensurate relief of pain and are associated with an appreciably increased incidence of undesirable side effects.

2.3 Cessation of Therapy

When the patient no longer requires therapy with codeine sulfate, doses should be tapered gradually to prevent signs and symptoms of withdrawal in the physically dependent patient.