Epoprostenol

FULL PRESCRIBING INFORMATION

Indications and Usage for Epoprostenol

Epoprostenol is indicated for:

• the long-term intravenous treatment of primary pulmonary hypertension


• and pulmonary hypertension associated with the scleroderma spectrum of disease in NYHA Class III and Class IV patients who do not respond adequately to conventional therapy


• [see CLINICAL STUDIES: Clinical Trials in Pulmonary Hypertension (14.1)].

Epoprostenol Dosage and Administration

Important Note: Epoprostenol for Injection must be reconstituted only as directed with Sterile Water for Injection, USP, or Sodium Chloride 0.9% Injection, USP. Reconstituted solutions of Epoprostenol for Injection must not be diluted or administered with other parenteral solutions or medications [see WARNINGS AND PRECAUTIONS: General (5.1)].

Dosage

Continuous chronic infusion of Epoprostenol should be prepared as directed [see Reconstitution (2.4)], and administered through a central venous catheter. Temporary peripheral intravenous infusion may be used until central access is established. Chronic infusion of Epoprostenol should be initiated at 2 ng/kg/min and increased in increments of 2 ng/kg/min every 15 minutes or longer until dose-limiting pharmacologic effects are elicited or until a tolerance limit to the drug is established or further increases in the infusion rate are not clinically warranted [see Dosage Adjustments (2.2)]. If dose-limiting pharmacologic effects occur, then the infusion rate should be decreased to the point that the pharmacologic effects of Epoprostenol are tolerated. In clinical trials, the most common dose-limiting adverse events were nausea, vomiting, hypotension, sepsis, headache, abdominal pain, or respiratory disorder (most treatment-limiting adverse events were not serious). If the initial infusion rate of 2 ng/kg/min is not tolerated, use a lower dose.

In the controlled 12-week trial in PH/SSD, for example, the dose increased from a mean starting dose of 2.2 ng/kg/min. During the first 7 days of treatment, the dose was increased daily to a mean dose of 4.1 ng/kg/min on day 7 of treatment. At the end of week 12, the mean dose was 11.2 ng/kg/min. The mean incremental increase was 2 to 3 ng/kg/min every 3 weeks.

Dosage Adjustments

Changes in the chronic infusion rate should be based on persistence, recurrence, or worsening of the patient's symptoms of pulmonary hypertension and the occurrence of adverse events due to excessive doses of Epoprostenol. In general, increases in dose from the initial chronic dose should be expected.

Increments in dose should be considered if symptoms of pulmonary hypertension persist or recur after improving. The infusion should be increased by 1- to 2-ng/kg/min increments at intervals sufficient to allow assessment of clinical response; these intervals should be at least 15 minutes. In clinical trials, incremental increases in dose occurred at intervals of 24 to 48 hours or longer. Following establishment of a new chronic infusion rate, the patient should be observed, and standing and supine blood pressure and heart rate monitored for several hours to ensure that the new dose is tolerated.

During chronic infusion, the occurrence of dose-limiting pharmacological events may necessitate a decrease in infusion rate, but the adverse event may occasionally resolve without dosage adjustment. Dosage decreases should be made gradually in 2-ng/kg/min decrements every 15 minutes or longer until the dose-limiting effects resolve. Abrupt withdrawal of Epoprostenol or sudden large reductions in infusion rates should be avoided. Except in life-threatening situations (e.g., unconsciousness, collapse, etc.), infusion rates of Epoprostenol should be adjusted only under the direction of a physician.

In patients receiving lung transplants, doses of Epoprostenol were tapered after the initiation of cardiopulmonary bypass.

Administration

Epoprostenol for Injection, once prepared as directed [see Reconstitution (2.4)], is administered by continuous intravenous infusion via a central venous catheter using an ambulatory infusion pump. During initiation of treatment, Epoprostenol may be administered peripherally.

The ambulatory infusion pump used to administer Epoprostenol should: (1) be small and lightweight, (2) be able to adjust infusion rates in 2-ng/kg/min increments, (3) have occlusion, end-of-infusion, and low-battery alarms, (4) be accurate to ±6% of the programmed rate, and (5) be positive pressure-driven (continuous or pulsatile) with intervals between pulses not exceeding 3 minutes at infusion rates used to deliver Epoprostenol. The reservoir should be made of polyvinyl chloride, polypropylene, or glass. The infusion pump used in the most recent clinical trials was the CADD-1 HFX 5100 (SIMS Deltec). A 60-inch microbore non-DEHP extension set with proximal antisyphon valve, low priming volume (0.9 mL), and in-line 0.22 micron filter was used during clinical trials.

To avoid potential interruptions in drug delivery, the patient should have access to a backup infusion pump and intravenous infusion sets. A multi-lumen catheter should be considered if other intravenous therapies are routinely administered.

Reconstitution

Epoprostenol for Injection is stable only when reconstituted as directed using Sterile Water for Injection, USP, or Sodium Chloride 0.9% Injection, USP. Epoprostenol for Injection must not be reconstituted or mixed with any other parenteral medications or solutions prior to or during administration.

Prior to use, Epoprostenol for Injection solutions reconstituted with 5 mL diluent must be protected from light and can be refrigerated at 2° to 8°C (36° to 46°F) for as long as 5 days or held at up to 25°C (77°F) for up to 48 hours prior to use. Do not freeze reconstituted solutions of Epoprostenol for Injection. Discard any reconstituted solution that has been frozen. Discard any reconstituted solution if it has been refrigerated for more than 5 days, or if held at room temperature for more than 48 hours.

During use, a single reservoir of diluted solution of Epoprostenol for Injection prepared as directed can be administered at room temperature for up to 24 hours. (If lower concentrations are chosen, pump reservoirs should be changed every 12 hours when administered at room temperature.) Do not expose this solution to direct sunlight.

A concentration for the solution of Epoprostenol should be selected that is compatible with the infusion pump being used with respect to minimum and maximum flow rates, reservoir capacity, and the infusion pump criteria listed above. Epoprostenol, when administered chronically, should be prepared in a drug delivery reservoir appropriate for the infusion pump. Outlined in Table 1 are directions for preparing different concentrations of Epoprostenol for up to a 24-hour period.

Table 1: Reconstitution and Dilution Instructions

To make 100 mL of solution with Final Concentration (ng/mL) of:	Directions:
* Higher concentrations may be prepared for patients who receive Epoprostenol long-term.
15,000 ng/mL*	Dissolve contents of one 1.5 mg vial with 5 mL of Sterile Water for Injection, USP, or Sodium Chloride 0.9% Injection, USP. Withdraw entire vial contents and add to a sufficient volume of the identical diluent to make a total of 100 mL.
30,000 ng/mL*	Dissolve contents of two 1.5 mg vials each with 5 mL of Sterile Water for Injection, USP, or Sodium Chloride 0.9% Injection, USP. Withdraw entire vial contents and add to a sufficient volume of the identical diluent to make a total of 100 mL.

Infusion rates may be calculated using the following formula:

Infusion Rate (mL/hr) =	[Dose (ng/kg/min) × Weight (kg) × 60 min/hr]
	Final Concentration (ng/mL)

Tables 2 and 3 provide infusion delivery rates for doses up to 16 ng/kg/min based upon patient weight, drug delivery rate, and concentration of the solution of Epoprostenol to be used. These tables may be used to select the most appropriate concentration of Epoprostenol that will result in an infusion rate between the minimum and maximum flow rates of the infusion pump and that will allow the desired duration of infusion from a given reservoir volume. For infusion/dose rates lower than those listed in Tables 2 and 3, it is recommended that the pump rate be set by a healthcare professional such that steady state is achieved in the patient, keeping in mind the half life of Epoprostenol is no more than six minutes. Higher infusion rates, and therefore, more concentrated solutions may be necessary with long-term administration of Epoprostenol. If lower concentrations are chosen, pump reservoirs should be changed every 12 hours when administered at room temperature.

Table 2: Infusion Rates for Epoprostenol at a Concentration of 15,000 ng/mL

	Dose or Drug Delivery Rate (ng/kg/min)
Patient weight (kg)	4	6	8	10	12	14	16
	Infusion Delivery Rate (mL/hr)
20	---	---	---	---	1.0	1.1	1.3
30	---	---	1.0	1.2	1.4	1.7	1.9
40	---	1.0	1.3	1.6	1.9	2.2	2.6
50	---	1.2	1.6	2.0	2.4	2.8	3.2
60	1.0	1.4	1.9	2.4	2.9	3.4	3.8
70	1.1	1.7	2.2	2.8	3.4	3.9	4.5
80	1.3	1.9	2.6	3.2	3.8	4.5	5.1
90	1.4	2.2	2.9	3.6	4.3	5.0	5.8
100	1.6	2.4	3.2	4.0	4.8	5.6	6.4

Table 3: Infusion Rates for Epoprostenol at a Concentration of 30,000 ng/mL

Dose or Drug Delivery Rate (ng/kg/min)
Patient weight (kg)	6	8	10	12	14	16
30	---	---	---	---	---	1.0
40	---	---	---	1.0	1.1	1.3
50	---	---	1.0	1.2	1.4	1.6
60	---	1.0	1.2	1.4	1.7	1.9
70	---	1.1	1.4	1.7	2.0	2.2
80	1.0	1.3	1.6	1.9	2.2	2.6
90	1.1	1.4	1.8	2.2	2.5	2.9
100	1.2	1.6	2.0	2.4	2.8	3.2

Dosage Forms and Strengths

Epoprostenol for Injection contains Epoprostenol sodium equivalent to 1.5 mg (1,500,000 ng) Epoprostenol and is supplied as a sterile lyophilized material in a 10 mL vial with a red flip-off seal.

Contraindications

A large study evaluating the effect of Epoprostenol on survival in NYHA Class III and IV patients with congestive heart failure due to severe left ventricular systolic dysfunction was terminated after an interim analysis of 471 patients revealed a higher mortality in patients receiving Epoprostenol plus conventional therapy than in those receiving conventional therapy alone. The chronic use of Epoprostenol in patients with congestive heart failure due to severe left ventricular systolic dysfunction is therefore contraindicated.

Some patients with pulmonary hypertension have developed pulmonary edema during dose initiation, which may be associated with pulmonary veno-occlusive disease. Epoprostenol should not be used chronically in patients who develop pulmonary edema during dose initiation.

Epoprostenol is also contraindicated in patients with known hypersensitivity to the drug or to structurally related compounds.

Warnings and Precautions

General

Epoprostenol for Injection must be reconstituted only as directed using Sterile Water for Injection, USP, or Sodium Chloride 0.9% Injection, USP. Epoprostenol for Injection must not be reconstituted or mixed with any other parenteral medications or solutions prior to or during administration. [See Reconstitution (2.4)]

Epoprostenol should be used only by clinicians experienced in the diagnosis and treatment of pulmonary hypertension. The diagnosis of pulmonary hypertension should be carefully established.

Dose Initiation

Epoprostenol is a potent pulmonary and systemic vasodilator. Dose initiation with Epoprostenol must be performed in a setting with adequate personnel and equipment for physiologic monitoring and emergency care. Dose initiation in controlled PPH clinical trials was performed during right heart catheterization. In clinical trials, dose initiation was performed without cardiac catheterization. The risk of cardiac catheterization in patients with pulmonary hypertension should be carefully weighed against the potential benefits. During dose initiation, asymptomatic increases in pulmonary artery pressure coincident with increases in cardiac output occurred rarely. In such cases, dose reduction should be considered, but such an increase does not imply that chronic treatment is contraindicated.

Chronic Use and Dose Adjustment

During chronic use, Epoprostenol is delivered continuously on an ambulatory basis through a permanent indwelling central venous catheter. Unless contraindicated, anticoagulant therapy should be administered to PPH and PH/SSD patients receiving Epoprostenol to reduce the risk of pulmonary thromboembolism or systemic embolism through a patent foramen ovale. In order to reduce the risk of infection, aseptic technique must be used in the reconstitution and administration of Epoprostenol as well as in routine catheter care. Because Epoprostenol is metabolized rapidly, even brief interruptions in the delivery of Epoprostenol may result in symptoms associated with rebound pulmonary hypertension including dyspnea, dizziness, and asthenia. The decision to initiate therapy with Epoprostenol should be based upon the understanding that there is a high likelihood that intravenous therapy with Epoprostenol will be needed indefinitely, and the patient's ability to accept and care for a permanent intravenous catheter and infusion pump should be carefully considered.

Based on clinical trials, the acute hemodynamic response (reduction in pulmonary artery resistance) to Epoprostenol did not correlate well with improvement in exercise tolerance or survival during chronic use of Epoprostenol. Dosage of Epoprostenol during chronic use should be adjusted at the first sign of recurrence or worsening of symptoms attributable to pulmonary hypertension or the occurrence of adverse events associated with Epoprostenol [see DOSAGE AND ADMINISTRATION (2)]. Following dosage adjustments, standing and supine blood pressure and heart rate should be monitored closely for several hours.

Withdrawal Effects

Abrupt withdrawal (including interruptions in drug delivery) or sudden large reductions in dosage of Epoprostenol may result in symptoms associated with rebound pulmonary hypertension, including dyspnea, dizziness, and asthenia. In clinical trials, one Class III primary pulmonary hypertension patient's death was judged attributable to the interruption of Epoprostenol. Abrupt withdrawal should be avoided.

Sepsis

See ADVERSE REACTIONS, Adverse Events Attributable to the Drug Delivery System (6.1).

Adverse Reactions

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

During clinical trials, adverse events were classified as follows: (1) adverse events during dose initiation and escalation, (2) adverse events during chronic dosing, and (3) adverse events associated with the drug delivery system.

Adverse Events During Dose Initiation and Escalation

During early clinical trials, Epoprostenol was increased in 2-ng/kg/min increments until the patients developed symptomatic intolerance. The most common adverse events and the adverse events that limited further increases in dose were generally related to vasodilation, the major pharmacologic effect of Epoprostenol. The most common dose-limiting adverse events (occurring in ≥1% of patients) were nausea, vomiting, headache, hypotension, and flushing, but also include chest pain, anxiety, dizziness, bradycardia, dyspnea, abdominal pain, musculoskeletal pain, and tachycardia. Table 4 lists the adverse events reported during dose initiation and escalation in decreasing order of frequency.

Table 4: Adverse Events During Dose Initiation and Escalation

Adverse Events Occurring in ≥1% of Patients	Epoprostenol (n = 391)
Flushing	58%
Headache	49%
Nausea/vomiting	32%
Hypotension	16%
Anxiety, nervousness, agitation	11%
Chest pain	11%
Dizziness	8%
Bradycardia	5%
Abdominal pain	5%
Musculoskeletal pain	3%
Dyspnea	2%
Back pain	2%
Sweating	1%
Dyspepsia	1%
Hypesthesia/paresthesia	1%
Tachycardia	1%

Adverse Events During Chronic Administration for PPH

Interpretation of adverse events is complicated by the clinical features of PPH and PH/SSD, which are similar to some of the pharmacologic effects of Epoprostenol (e.g., dizziness, syncope). Adverse events probably related to the underlying disease include dyspnea, fatigue, chest pain, edema, hypoxia, right ventricular failure, and pallor. Several adverse events, on the other hand, can clearly be attributed to Epoprostenol. These include headache, jaw pain, flushing, diarrhea, nausea and vomiting, flu-like symptoms, and anxiety/nervousness.

In an effort to separate the adverse effects of the drug from the adverse effects of the underlying disease, Table 5 lists adverse events that occurred at a rate at least 10% different in the 2 groups in controlled trials for PPH.

Table 5: Adverse Events Regardless of Attributions Occurring in Patients With PPH With ≥ 10% Difference Between Epoprostenol and Conventional Therapy Alone

Adverse Event	Epoprostenol (n = 52)	Conventional Therapy (n = 54)
Occurrence More Common With Epoprostenol
General
Chills/fever/sepsis/flu-like symptoms	25%	11%
Cardiovascular
Tachycardia	35%	24%
Flushing	42%	2%
Gastrointestinal
Diarrhea	37%	6%
Nausea/vomiting	67%	48%
Musculoskeletal
Jaw pain	54%	0%
Myalgia	44%	31%
Nonspecific musculoskeletal pain	35%	15%
Neurological
Anxiety/nervousness/tremor	21%	9%
Dizziness	83%	70%
Headache	83%	33%
Hypesthesia, hyperesthesia, paresthesia	12%	2%
Occurrence More Common With Standard Therapy
Cardiovascular
Heart failure	31%	52%
Syncope	13%	24%
Shock	0%	13%
Respiratory
Hypoxia	25%	37%

Thrombocytopenia has been reported during uncontrolled clinical trials in patients receiving Epoprostenol.

Table 6 lists additional adverse events reported in PPH patients receiving Epoprostenol plus conventional therapy or conventional therapy alone during controlled clinical trials.

Table 6: Adverse Events Regardless of Attribution Occurring In Patients with PPH With <10% Difference between Epoprostenol and Conventional Therapy

Adverse Event	Epoprostenol (n = 52)	Conventional Therapy (n = 54)
General
Asthenia	87%	81%
Cardiovascular
Angina pectoris	19%	20%
Arrhythmia	27%	20%
Bradycardia	15%	9%
Supraventricular tachycardia	8%	0%
Pallor	21%	30%
Cyanosis	31%	39%
Palpitation	63%	61%
Cerebrovascular accident	4%	0%
Hemorrhage	19%	11%
Hypotension	27%	31%
Myocardial ischemia	2%	6%
Gastrointestinal
Abdominal Pain	27%	31%
Anorexia	25%	30%
Ascites	12%	17%
Constipation	6%	2%
Metabolic
Edema	60%	63%
Hypokalemia	6%	4%
Weight reduction	27%	24%
Weight gain	6%	4%
Musculoskeletal
Arthralgia	6%	0%
Bone pain	0%	4%
Chest pain	67%	65%
Neurological
Confusion	6%	11%
Convulsion	4%	0%
Depression	37%	44%
Insomnia	4%	4%
Respiratory
Cough increase	38%	46%
Dyspnea	90%	85%
Epistaxis	4%	2%
Pleural effusion	4%	2%
Skin and Appendages
Pruritus	4%	0%
Rash	10%	13%
Sweating	15%	20%
Special Senses
Amblyopia	8%	4%
Vision abnormality	4%	0%

Adverse Events During Chronic Administration for PH/SSD

In an effort to separate the adverse effects of the drug from the adverse effects of the underlying disease, Table 7 lists adverse events that occurred at a rate at least 10% different in the 2 groups in the controlled trial for patients with PH/SSD.

Table 7: Adverse Events Regardless of Attribution Occurring in Patients With PH/SSD With ≥10% Difference Between Epoprostenol and Conventional Therapy Alone

Adverse Event	Epoprostenol (n = 56)	Conventional Therapy (n = 55)
Occurrence More Common With Epoprostenol
Cardiovascular
Flushing	23%	0%
Hypotension	13%	0%
Gastrointestinal
Anorexia	66%	47%
Nausea/vomiting	41%	16%
Diarrhea	50%	5%
Musculoskeletal
Jaw pain	75%	0%
Pain/neck pain/arthralgia	84%	65%
Neurological
Headache	46%	5%
Skin and Appendages
Skin ulcer	39%	24%
Eczema/rash/urticaria	25%	4%
Occurrence More Common With Conventional Therapy
Cardiovascular
Cyanosis	54%	80%
Pallor	32%	53%
Syncope	7%	20%
Gastrointestinal
Ascites	23%	33%
Esophageal reflux/gastritis	61%	73%
Metabolic
Weight decrease	45%	56%
Neurological
Dizziness	59%	76%
Respiratory
Hypoxia	55%	65%

Table 8 lists additional adverse events reported in PH/SSD patients receiving Epoprostenol plus conventional therapy or conventional therapy alone during controlled clinical trials.

Table 8: Adverse Events Regardless of Attribution Occurring in Patients With PH/SSD With <10% Difference Between Epoprostenol and Conventional Therapy Alone

Adverse Event*	Epoprostenol (n = 56)	Conventional Therapy (n = 55)
* Adverse events that occurred in at least 2 patients in either treatment group.
General
Asthenia	100%	98%
Hemorrhage/hemorrhage injection site/hemorrhage rectal	11%	2%
Infection/rhinitis	21%	20%
Chills/fever/sepsis/flu-like symptoms	13%	11%
Blood and Lymphatic
Thrombocytopenia	4%	0%
Cardiovascular
Heart failure/heart failure right	11%	13%
Myocardial Infarction	4%	0%
Palpitation	63%	71%
Shock	5%	5%
Tachycardia	43%	42%
Vascular disorder peripheral	96%	100%
Vascular disorder	95%	89%
Gastrointestinal
Abdominal enlargement	4%	0%
Abdominal pain	14%	7%
Constipation	4%	2%
Flatulence	5%	4%
Metabolic
Edema/edema peripheral/edema genital	79%	87%
Hypercalcemia	48%	51%
Hyperkalemia	4%	0%
Thirst	0%	4%
Musculoskeletal
Arthritis	52%	45%
Back pain	13%	5%
Chest pain	52%	45%
Cramps leg

Zinacef

1. Name Of The Medicinal Product

Zinacef®

Cefuroxime (as sodium) INN for Injection or Infusion.

2. Qualitative And Quantitative Composition

Vials contain either 250mg, 750mg or 1.5g cefuroxime (as sodium).

3. Pharmaceutical Form

Cefuroxime is a white to cream powder to which appropriate amounts of water are added to prepare an off-white suspension for intramuscular use or a yellowish solution for intravenous administration.

4. Clinical Particulars

4.1 Therapeutic Indications

Zinacef is a bactericidal cephalosporin antibiotic which is resistant to most beta-lactamases and is active against a wide range of Gram-positive and Gram-negative organisms. It is indicated for the treatment of infections before the infecting organism has been identified or when caused by sensitive bacteria. In addition, it is an effective prophylactic against post-operative infection in a variety of operations. Usually Zinacef will be effective alone, but when appropriate it may be used in combination with an aminoglycoside antibiotic, or in conjunction with metronidazole, orally or by suppository or injection, (see Pharmaceutical precautions).

In situations where mixed aerobic and anaerobic infections are encountered or suspected (e.g. peritonitis, aspiration pneumonia, abscesses in the lung, pelvis and brain), or are likely to occur (e.g. in association with colorectal or gynaecological surgery) it is appropriate to administer Zinacef in combination with metronidazole.

Most of these infections will respond to an i.v. regimen of Zinacef (750mg) plus metronidazole injection (500mg/100ml) administered eight-hourly. In more severe or well established mixed infections, an i.v. regimen of Zinacef (1.5g) plus metronidazole injection (500mg/100ml) eight-hourly may be indicated. For the prophylaxis of infection in surgery (e.g. colorectal and gynaecological) a single dose of 1.5g Zinacef plus metronidazole injection (500mg/100ml) is appropriate.

Alternatively this may be followed by two 750mg doses of Zinacef plus metronidazole.

Indications include:

Respiratory tract infections for example, acute and chronic bronchitis, infected bronchiectasis, bacterial pneumonia, lung abscess and post operative chest infections.

Ear, nose and throat infections for example, sinusitis, tonsillitis and pharyngitis.

Urinary tract infections for example acute and chronic pyelonephritis, cystitis and asymptomatic bacteriuria.

Soft-tissue infections for example cellulitis, erysipelas, peritonitis and wound infections.

Bone and joint infections for example, osteomyelitis and septic arthritis.

Obstetric and gynaecological infections pelvic inflammatory diseases.

Gonorrhoea particularly when penicillin is unsuitable.

Other infections including septicaemia and meningitis.

Prophylaxis against infection in abdominal, pelvic, orthopaedic, cardiac, pulmonary, oesophageal and vascular surgery where there is increased risk from infection.

Cefuroxime is also available as the axetil ester (Zinnat) for oral administration.

This permits the use of sequential therapy with the same antibiotic, when a change from parenteral to oral therapy is clinically indicated. Where appropriate Zinacef is effective when used prior to oral therapy with Zinnat (cefuroxime axetil) in the treatment of pneumonia and acute exacerbations of chronic bronchitis.

4.2 Posology And Method Of Administration

Intramuscular

Add 1ml water for injections to 250mg Zinacef or 3ml water for injections to 750mg Zinacef. Shake gently to produce an opaque suspension.

Intravenous

Dissolve Zinacef in water for injections using at least 2ml for 250mg, at least 6ml for 750mg or 15ml for 1.5g. For short intravenous infusion (e.g. up to 30 minutes), 1.5g may be dissolved in 50ml water for injections. These solutions may be given directly into the vein or introduced into the tubing of the giving set if the patient is receiving parenteral fluids.

General Recommendations

Adults: Many infections will respond to 750mg t.i.d. by im or iv injection. For more severe infections, this dose should be increased to 1.5g t.i.d. iv. The frequency of im or iv injection can be increased to six-hourly if necessary, giving total doses of 3g to 6g daily.

Where clinically indicated adults with pneumonia and acute exacerbations of chronic bronchitis have been shown to respond to 750mg or 1.5g bd, followed by oral therapy with Zinnat (see Sequential therapy).

Infants and Children: Doses of 30 to 100mg/kg/day given as three or four divided doses. A dose of 60mg/kg/day will be appropriate for most infections.

Neonates: Doses of 30 to 100mg/kg/day given as two or three divided doses. In the first weeks of life the serum half-life of cefuroxime can be three to five times that in adults.

Elderly: See dosage in adults.

Other Recommendations

Gonorrhoea: 1.5g should be given as a single dose. This may be given as 2 x 750mg injections into different sites eg each buttock.

Meningitis: Zinacef is suitable for sole therapy of bacterial meningitis due to sensitive strains. The following dosages are recommended.

Infants and Children: 200 to 240mg/kg/day iv in three or four divided doses. This dosage may be reduced to 100mg/kg/day iv after three days or when clinical improvement occurs.

Neonates: The initial dosage should be 100mg/kg/day iv. A reduction to 50mg/kg/day iv may be made when clinically indicated.

Adults: 3g iv every eight hours. Data are not yet sufficient to recommend a dose for intrathecal administration.

Prophylaxis: The usual dose is 1.5g iv with induction of anaethesia for abdominal, pelvic and orthopaedic operations, but may be supplemented with two 750mg im doses eight and sixteen hours later. In cardiac pulmonary oesophageal and vascular operations, the usual dose is 1.5g iv with induction of anaesthesia continuing with 750mg im t.d.s. for a further 24 to 48 hours.

In total joint replacement, 1.5g cefuroxime powder may be mixed dry with each pack of methyl methacrylate cement polymer before adding the liquid monomer.

Sequential therapy:

Pneumonia:

1.5g bd (iv or im) for 48-72 hours, followed by 500mg bd Zinnat (cefuroxime axetil) oral therapy for 7 days.

Acute exacerbations of chronic bronchitis:

750mg bd (iv or im) for 48-72 hours, followed by 500mg bd Zinnat (cefuroxime axetil) oral therapy for 5-7 days.

Duration of both parenteral and oral therapy is determined by the severity of the infection and the clinical status of the patient.

Dosage in impaired renal function

Cefuroxime is excreted by the kidneys. Therefore, as with all such antibiotics, in patients with markedly impaired renal function it is recommended that the dosage of Zinacef should be reduced to compensate for its slower excretion. However, it is not necessary to reduce the dose until the creatinine clearance falls below 20ml/min. In adults with marked impairment (creatinine clearance 10-20ml/min) 750mg bd is recommended and with severe impairment (creatinine clearance <10ml/min) 750mg once daily is adequate. For patients on haemodialysis a further 750mg dose should be given at the end of each dialysis. When continuous peritoneal dialysis is being used, a suitable dosage is usually 750mg twice daily.

For patients in renal failure on continuous arteriovenous haemodialysis or high-flux haemofiltration in intensive therapy units a suitable dosage is 750mg twice daily. For low-flux haemofiltration follow the dosage recommended under impaired renal function.

Cefuroxime is also available as the axetil ester (Zinnat) for oral administration. This permits parenteral therapy with cefuroxime to be followed by oral therapy in situations where a change from parenteral to oral is clinically indicated.

4.3 Contraindications

Hypersensitivity to cephalosporin antibiotics

4.4 Special Warnings And Precautions For Use

Special care is indicated in patients who have experienced an allergic reaction to penicillins or beta-lactams.

Cephalosporin antibiotics at high dosage should be given with caution to patients receiving concurrent treatment with potent diuretics such as furosemide or aminoglycosides, as renal impairment has been reported with these combinations. Renal function should be monitored in these patients, the elderly, and those with pre-existing renal impairment (See section 4.2) Clinical experience with Zinacef has shown that this is not likely to be a problem at the recommended dose levels.

There may be some variation on the results of biochemical tests of renal function, but these do not appear to be of clinical importance. As a precaution, renal function should be monitored if this is already impaired.

Delayed sterilisation of the CSF in patients with Haemophilus influenzae meningitis may result in an adverse outcome such as deafness and /or neurological sequelae. Persistence of positive CSF cultures of H. influenzae at 18-36 hours has been noted in some patients treated with cefuroxime sodium injection and, as with other therapeutic regimens used in the treatment of meningitis, hearing loss has been reported in some children.

With a sequential therapy regime the timing of change to oral therapy is determined by severity of the infection, clinical status of the patient and susceptibility of the pathogens involved. The change to oral therapy should only be made once there is a clear clinical improvement. If there has been no clinical improvement after 72 hours of parenteral treatment, then the patient's treatment should be reviewed. Please refer to the relevant prescribing information for cefuroxime axetil before initiating sequential therapy.

As with other antibiotics, prolonged use of cefuroxime may result in the overgrowth of non-susceptible organisms (e.g. Candida, enterococci, Clostridium difficile), which may require interruption of treatment.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

In common with other antibiotics, Zinacef may affect the gut flora, leading to lower oestrogen reabsorption and reduced efficacy of combined oral contraceptives.

As with other cephalosporin antibiotics in combination with potent diuretics such as furosemide or aminoglycosides, Zinacef may adversely affect renal function (See section 4.4).

Zinacef does not interfere in enzyme-based tests for glycosuria. Slight interference with copper reduction methods (Benedict's, Fehling's, Clinitest) may be observed. However, this should not lead to false-positive results, as may be experienced with some other cephalosporins.

It is recommended that either the glucose oxidase or hexokinase methods are used to determine blood/plasma glucose levels in patients receiving Zinacef. This antibiotic does not interfere in the alkaline picrate assay for creatinine.

4.6 Pregnancy And Lactation

There is no experimental evidence of embryopathic or teratogenic effects attributable to Zinacef but, as with all drugs, it should be administered with caution during the early months of pregnancy.

Cefuroxime is excreted in human milk, and consequently caution should be exercised when Zinacef is administered to a nursing mother.

4.7 Effects On Ability To Drive And Use Machines

None reported.

4.8 Undesirable Effects

Adverse drug reactions are very rare (<1/10,000) and are generally mild and transient in nature.

The frequency categories assigned to the adverse reactions below are estimates, as for most reactions suitable data for calculating incidence are not available. In addition the incidence of adverse reactions associated with cefuroxime sodium may vary according to the indication.

Data from clinical trials were used to determine the frequency of very common to rare undesirable effects. The frequencies assigned to all other undesirable effects (i.e., those occurring at <1/1000) were mainly determined using post-marketing data, and refer to a reporting rate rather than a true frequency.

The following convention has been used for the classification of frequency:

very common

Infections and infestations
Rare	Candida overgrowth from prolonged use.

Blood and lymphatic system disorders
Common	Neutropenia, eosinophilia.
Uncommon	Leukopenia, decreased haemoglobin concentration, positive Coomb's test.
Rare	Thrombocytopenia.
Very rare	Haemolytic anaemia.

Cephalosporins as a class tend to be absorbed onto the surface of red cell membranes and react with antibodies directed against the drug to produce a positive Coomb's Test (which can interfere with cross matching of blood) and very rarely haemolytic anaemia.

Immune system disorders Hypersensitivity reactions including
Uncommon	Skin rash, urticaria and pruritus.
Rare	Drug fever.
Very rare	Interstitial nephritis, anaphylaxis, cutaneous vasculitis

See also Skin and subcutaneous tissue disorders and Renal and urinary disorders.

Gastrointestinal disorders
Uncommon	Gastrointestinal disturbance.
Very rare	Pseudomembranous colitis.

Hepatobiliary disorders
Common	Transient rise in liver enzymes.
Uncommon	Transient rise in bilirubin.

Transient rises in serum liver enzymes or bilirubin occur, particularly in patients with pre-existing liver disease, but there is no evidence of harm to the liver.

Skin and subcutaneous tissue disorders
Very rare	Erythema multiforme, toxic epidermal necrolysis and Stevens Johnson Syndrome.

See also Immune system disorders.

Renal and urinary disorders
Very rare	Elevations in serum creatinine, elevations in blood urea nitrogen and decreased creatinine clearance (See Section 4.4 Special Warnings and Precautions for use ).

See also Immune system disorders.

General disorders and administration site conditions
Common	Injection site reactions which may include pain and thrombophlebitis

Pain at the intramuscular injection site is more likely at higher doses. However it is unlikely to be a cause for discontinuation of treatment.

4.9 Overdose

Overdosage of cephalosporins can cause cerebral irritation leading to convulsions. Serum levels of cefuroxime can be reduced by haemodialysis or peritoneal dialysis.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Cefuroxime is a bactericidal cephalosporin antibiotic which is resistant to most beta-lactamases and is active against a wide range of Gram-positive and Gram-negative organisms.

It is highly active against Staphylococcus aureus, including strains which are resistant to penicillin (but not the rare methicillin-resistant strains), Staph. epidermidis, Haemophilus influenzae, Klebsiella spp., Enterobacter spp., Streptococcus pyogenes, Escherichia coli, Str. mitis (viridans group), Clostridium spp., Proteus mirabilis, Pr. rettgeri, Salmonella typhi, S. typhimurium and other Salmonella spp., Shigella spp., Neisseria spp. (including beta-lactamase producing strains of N. gonorrhoea) and Bordetella pertussis. It is also moderately active against strains of Pr. vulgaris, Morganella morganii (formerly Proteus morganii) and Bacteroides fragilis.

The following organisms are not susceptible to cefuroxime: Clostridium difficile, Pseudomonas spp., Campylobacter spp., Acinetobacter calcoaceticus, Legionella spp. and methicillin-resistant strains of Staph. aureus and Staph. epidermidis.

Some strains of the following genera have also been found not to be susceptible to Zinacef:

Strep. faecalis, Morganella morganii, Proteus vulgaris, Enterobacter spp., Citrobacter spp., Serratia spp. and Bacteroides fragilis.

In vitro the activities of Zinacef and aminoglycoside antibiotics in combination have been shown to be at least additive with occasional evidence of synergy.

5.2 Pharmacokinetic Properties

Peak levels of cefuroxime are achieved within 30 to 45 minutes after intramuscular administration. The serum half-life after either intramuscular or intravenous injection is approximately 70 minutes. Concurrent administration of probenecid prolongs the excretion of the antibiotic and produces an elevated peak serum level. There is almost complete recovery of unchanged cefuroxime in the urine within 24 hours of administration, the major part being eliminated in the first six hours. Approximately 50% is excreted through the renal tubules and approximately 50% by glomerular filtration. Concentrations of cefuroxime in excess of the minimum inhibitory levels for common pathogens can be achieved in bone, synovial fluid and aqueous humor. Cefuroxime passes the blood-brain barrier when the meninges are inflamed.

5.3 Preclinical Safety Data

None stated

6. Pharmaceutical Particulars

6.1 List Of Excipients

None.

6.2 Incompatibilities

Cefuroxime is compatible with most commonly used intravenous fluids and electrolyte solutions.

The pH of 2.74% w/v sodium bicarbonate injection BP considerably affects the colour of solutions and therefore this solution is not recommended for the dilution of Zinacef. However, if required, for patients receiving sodium bicarbonate injection by infusion the Zinacef may be introduced into the tube of the giving set.

Zinacef should not be mixed in the syringe with aminoglycoside antibiotics.

6.3 Shelf Life

Two years when stored below 25ºC and protected from light.

6.4 Special Precautions For Storage

Store below 25ºC and protect from light.

After constitution, Zinacef should be stored at 2 - 8ºC for no longer than 24 hours.

6.5 Nature And Contents Of Container

1) Moulded glass (type 1 or III) vials with bromobutyl or fluoro-resin laminated butyl rubber plug, overseal and flip-off cap containing either 250mg, 750mg or 1.5g Zinacef.

2) A bulk pack of 100 vials.

3) Monovial containing either 750mg or 1.5g Zinacef with transfer needle.

*Only the 1.5g injection pack is marketed (the infusion pack is not)

6.6 Special Precautions For Disposal And Other Handling

None.

Administrative Data

7. Marketing Authorisation Holder

Glaxo Operations UK Limited, Greenford, Middlesex UB6 0HE

Trading as

GlaxoSmithKline UK, Stockley Park West, Uxbridge, Middlesex UB11 1BT

8. Marketing Authorisation Number(S)

PL 00004/0263.

9. Date Of First Authorisation/Renewal Of The Authorisation

28 April 2002

10. Date Of Revision Of The Text

17th November 2008

11. Legal Status

POM

Votrient

Generic Name: pazopanib (paz OH pa nib)

Brand Names: Votrient

What is pazopanib?

Pazopanib is a cancer medication that interferes with the growth of cancer cells and slows their spread in the body.

Pazopanib is used to treat advanced renal cell carcinoma (kidney cancer).

Pazopanib may also be used for purposes not listed in this medication guide.

What is the most important information I should know about pazopanib?

Do not use pazopanib if you are pregnant. It could harm the unborn baby.

Before you take pazopanib, tell your doctor if you have liver disease, heart disease, high blood pressure, underactive thyroid, an ulcer or other stomach disorder, or a history of Long QT syndrome, blood clot, or bleeding (stomach, intestinal, or brain).

There are many other drugs that can interact with pazopanib. Tell your doctor about all medications you use.

To be sure this medication is not causing harmful effects, your blood may need to be tested often. Visit your doctor regularly.

If you need surgery, tell the surgeon ahead of time that you are using pazopanib. You may need to stop using the medicine for a short time. Stop using pazopanib and call your doctor at once if you have a serious side effect such as bloody or tarry stools, coughing up blood, loss of appetite, dark urine, jaundice (yellowing of the skin or eyes), sudden numbness or weakness, problems with speech or balance, chest pain, or vision and hearing problems.

What should I discuss with my health care provider before taking pazopanib?

You should not use this medication if you are allergic to it.

To make sure you can safely take pazopanib, tell your doctor if you have any of these other conditions:

• liver disease;


• 
  

  heart disease;

  
  


• 
  

  high blood pressure;

  
  


• 
  

  a personal or family history of Long QT syndrome;

  
  


• 
  

  a history of blood clot;

  
  


• 
  

  underactive thyroid;

  
  


• 
  

  an ulcer or other stomach disorder;

  
  


• 
  

  a head injury or bleeding in your brain within the past 6 months; or

  
  


• 
  

  stomach or intestinal bleeding within the past 6 months.

  
  

FDA pregnancy category D. Do not use pazopanib if you are pregnant. It could harm the unborn baby. Use effective birth control, and tell your doctor if you become pregnant during treatment. It is not known whether pazopanib passes into breast milk or if it could harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

How should I take pazopanib?

Take exactly as prescribed by your doctor. Do not take in larger or smaller amounts or for longer than recommended. Follow the directions on your prescription label.

Take pazopanib on an empty stomach, at least 1 hour before or 2 hours after a meal.

Pazopanib is usually taken once per day. Your doctor may occasionally change your dose to make sure you get the best results.

Do not crush a pazopanib tablet. Swallow the pill whole. Crushing the pill may cause your body to absorb too much of the drug at one time. The medicine from a crushed or broken pill can be dangerous if it gets on your skin. If this occurs, wash your skin with soap and water and rinse thoroughly. To be sure this medication is not causing harmful effects, your blood and urine may need to be tested often. Your heart rate may also need to be checked using an electrocardiograph or ECG (sometimes called an EKG). Visit your doctor regularly. If you need surgery, tell the surgeon ahead of time that you are using pazopanib. You may need to stop using the medicine for a short time. Store at room temperature away from moisture and heat.

What happens if I miss a dose?

Take the missed dose as soon as you remember. Skip the missed dose if your next dose is less than 12 hours away. Do not take extra medicine to make up the missed dose.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Overdose symptoms may include extreme tiredness or high blood pressure (severe headache, hearing or vision problems, anxiety, chest pain, shortness of breath, uneven heartbeats).

What should I avoid while taking pazopanib?

Follow your doctor's instructions about any restrictions on food, beverages, or activity.

Pazopanib side effects

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat. Stop using pazopanib and call your doctor at once if you have a serious side effect such as:

• 
  

  slow healing of a wound or surgical incision;

  
  


• 
  

  dizziness, fainting, fast or pounding heartbeat;

  
  


• 
  

  black, bloody, or tarry stools;

  
  


• 
  

  coughing up blood or vomit that looks like coffee grounds;

  
  


• 
  

  nausea, upper stomach pain, itching, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes);

  
  


• 
  

  sudden numbness or weakness (especially on one side of the body), sudden severe headache, confusion, problems with vision, speech, or balance;

  
  


• 
  

  chest pain or heavy feeling, pain spreading to the arm or shoulder; or

  
  


• 
  

  dangerously high blood pressure (severe headache, blurred vision, buzzing in your ears, anxiety, shortness of breath, uneven heartbeats, seizure).

  
  

Less serious side effects may include:

• 
  

  mild nausea or vomiting, diarrhea;

  
  


• 
  

  changes in hair color;

  
  


• 
  

  tired feeling; or

  
  


• 
  

  headache.

  
  

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

What other drugs will affect pazopanib?

Many drugs can interact with pazopanib. Below is just a partial list. Tell your doctor if you are using:

• 
  

  ADHD medications;

  
  


• 
  

  an antibiotic or antifungal medication;

  
  


• 
  

  an antidepressant or medicine to treat a psychiatric disorder;

  
  


• 
  

  anti-malaria medications;

  
  


• 
  

  asthma or allergy medication;

  
  


• 
  

  cholesterol-lowering drugs;

  
  


• 
  

  diabetes medication you take by mouth;

  
  


• 
  

  drugs to treat erectile dysfunction;

  
  


• 
  

  heart or blood pressure medications, heart rhythm medication;

  
  


• 
  

  HIV or AIDS medications;

  
  


• 
  

  medicines used to prevent organ transplant rejection;

  
  


• 
  

  medicine to treat or prevent nausea and vomiting;

  
  


• 
  

  migraine headache medicines, including ergot medicines or "triptans";

  
  


• 
  

  other cancer medications;

  
  


• 
  

  sedatives or narcotic pain medication;

  
  


• 
  

  seizure medication; or

  
  


• 
  

  a steroid.

  
  

This list is not complete and there are many other drugs that can interact with pazopanib. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor. Keep a list of all your medicines and show it to any healthcare provider who treats you.

More Votrient resources

• Votrient Side Effects (in more detail)
• Votrient Use in Pregnancy & Breastfeeding
• Votrient Drug Interactions
• Votrient Support Group
• 7 Reviews for Votrient - Add your own review/rating

• Votrient Prescribing Information (FDA)


• Votrient Monograph (AHFS DI)


• Votrient Advanced Consumer (Micromedex) - Includes Dosage Information


• Votrient Consumer Overview


• Votrient MedFacts Consumer Leaflet (Wolters Kluwer)


• Pazopanib Professional Patient Advice (Wolters Kluwer)

Compare Votrient with other medications

• Renal Cell Carcinoma

Where can I get more information?

• Your pharmacist can provide more information about pazopanib.

See also: Votrient side effects (in more detail)

Erythrocin Stearate

Generic Name: erythromycin (Oral route, Parenteral route)

e-rith-roe-MYE-sin

Commonly used brand name(s)

In the U.S.

• E.E.S. 200


• E.E.S. 400


• E.E.S. Granules


• Eryped


• Eryped 200


• Eryped 400


• Erythrocin


• Erythrocin Stearate


• Ilosone

In Canada

• E.E.S. 100


• Ees 200


• Novo-Rythro Estolate Suspension


• Novo-Rythro Ethyl Succinate Suspension


• Novo-Rythro Stearate

Available Dosage Forms:

• Suspension


• Powder for Suspension


• Tablet


• Tablet, Chewable


• Capsule

Uses For Erythrocin Stearate

Erythromycins are used to treat many kinds of infections. Erythromycins are also used to prevent "strep" infections in patients with a history of rheumatic heart disease who may be allergic to penicillin.

These medicines may also be used to treat Legionnaires' disease and for other problems as determined by your doctor. They will not work for colds, flu, or other virus infections.

Erythromycins are available only with your doctor's prescription.

Once a medicine has been approved for marketing for a certain use, experience may show that it is also useful for other medical problems. Although these uses are not included in product labeling, erythromycins are used in certain patients with the following medical conditions:

• Acne


• Actinomycosis


• Anthrax


• Chancroid


• Gastroparesis


• Lyme disease


• Lymphogranuloma venereum


• Relapsing fever

Before Using Erythrocin Stearate

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to medicines in this group or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

This medicine has been tested in children and, in effective doses, has not been shown to cause different side effects or problems in children than it does in adults.

Geriatric

This medicine has been tested and has not been shown to cause different side effects or problems in older people than it does in younger adults. However, older adults may be at increased risk of hearing loss, especially if they are taking high doses of erythromycin and/or have kidney or liver disease.

Pregnancy

Erythromycin estolate has caused side effects involving the liver in some pregnant women. However, none of the erythromycins has been shown to cause birth defects or other problems in human babies.

Breast Feeding

Erythromycins pass into the breast milk. However, erythromycins have not been shown to cause problems in nursing babies.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. Tell your healthcare professional if you are taking any other prescription or nonprescription (over-the-counter [OTC]) medicine.

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of medicines in this class. Make sure you tell your doctor if you have any other medical problems, especially:

• Heart disease—High doses of erythromycin may increase the chance of side effects in patients with a history of an irregular heartbeat.

• Liver disease—Erythromycins, especially erythromycin estolate, may increase the chance of side effects involving the liver.

• Loss of hearing—High doses of erythromycins may, on rare occasion, cause hearing loss, especially if you have kidney or liver disease.

Proper Use of erythromycin

This section provides information on the proper use of a number of products that contain erythromycin. It may not be specific to Erythrocin Stearate. Please read with care.

Generally, erythromycins are best taken with a full glass (8 ounces) of water on an empty stomach (at least 1 hour before or 2 hours after meals). If stomach upset occurs, these medicines may be taken with food. If you have questions about the erythromycin medicine you are taking, check with your health care professional.

For patients taking the oral liquid form of this medicine:

• This medicine is to be taken by mouth even if it comes in a dropper bottle. If this medicine does not come in a dropper bottle, use a specially marked measuring spoon or other device to measure each dose accurately. The average household teaspoon may not hold the right amount of liquid


• Do not use after the expiration date on the label. The medicine may not work properly after that date. Check with your pharmacist if you have any questions about this.

For patients taking the chewable tablet form of this medicine:

• Tablets must be chewed or crushed before they are swallowed.

For patients taking the delayed-release capsule form (with enteric-coated pellets) or the delayed-release tablet form of this medicine:

• Swallow capsules or tablets whole. Do not break or crush. If you are not sure about which type of capsule or tablet you are taking, check with your pharmacist.

To help clear up your infection completely, keep taking this medicine for the full time of treatment, even if you begin to feel better after a few days. If you have a "strep" infection, you should keep taking this medicine for at least 10 days. This is especially important in "strep" infections. Serious heart problems could develop later if your infection is not cleared up completely. Also, if you stop taking this medicine too soon, your symptoms may return.

This medicine works best when there is a constant amount in the blood. To help keep the amount constant, do not miss any doses. Also, it is best to take the doses at evenly spaced times day and night. For example, if you are to take 4 doses a day, the doses should be spaced about 6 hours apart. If this interferes with your sleep or other daily activities, or if you need help in planning the best times to take your medicine, check with your health care professional.

Dosing

The dose medicines in this class will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of these medicines. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For erythromycin base


• For oral dosage forms (capsules, tablets):
  
  • For treatment of infections:
    
    • Adults and teenagers—250 to 500 milligrams (mg) two to four times a day.
    
    
    • Children—Dose is based on body weight. The usual dose is 7.5 to 12.5 mg per kilogram (kg) (3.4 to 5.6 mg per pound) of body weight four times a day, or 15 to 25 mg per kg (6.8 to 11.4 mg per pound) of body weight two times a day.
    
    
  
  
  • For prevention of heart infections:
    
    • Adults and teenagers—Take 1 gram two hours before your dental appointment or surgery, then 500 mg six hours after taking the first dose.
    
    
    • Children—Dose is based on body weight. The usual dose is 20 mg per kg (9.1 mg per pound) of body weight two hours before the dental appointment or surgery, then 10 mg per kg (4.5 mg per pound) of body weight six hours after taking the first dose.
    
    
  
  

• For erythromycin estolate


• For oral dosage forms (capsules, oral suspension, tablets):
  
  • For treatment of infections:
    
    • Adults and teenagers—250 to 500 milligrams (mg) two to four times a day.
    
    
    • Children—Dose is based on body weight. The usual dose is 7.5 to 12.5 mg per kilogram (kg) (3.4 to 5.6 mg per pound) of body weight four times a day, or 15 to 25 mg per kg (6.8 to 11.4 mg per pound) of body weight two times a day.
    
    
  
  
  • For prevention of heart infections:
    
    • Adults and teenagers—Take 1 gram two hours before your dental appointment or surgery, then 500 mg six hours after taking the first dose.
    
    
    • Children—Dose is based on body weight. The usual dose is 20 mg per kg (9.1 mg per pound) of body weight two hours before the dental appointment or surgery, then 10 mg per kg (4.5 mg per pound) of body weight six hours after taking the first dose.
    
    
  
  

• For erythromycin ethylsuccinate


• For oral dosage forms (oral suspension, tablets):
  
  • For treatment of infections:
    
    • Adults and teenagers—400 to 800 milligrams (mg) two to four times a day.
    
    
    • Children—Dose is based on body weight. The usual dose is 7.5 to 12.5 mg per kilogram (kg) (3.4 to 5.6 mg per pound) of body weight four times a day, or 15 to 25 mg per kg (6.8 to 11.4 mg per pound) of body weight two times a day.
    
    
  
  
  • For prevention of heart infections:
    
    • Adults and teenagers—Take 1.6 grams two hours before your dental appointment or surgery, then 800 mg six hours after taking the first dose.
    
    
    • Children—Dose is based on body weight. The usual dose is 20 mg per kg (9.1 mg per pound) of body weight two hours before the dental appointment or surgery, then 10 mg per kg (4.5 mg per pound) of body weight six hours after taking the first dose.
    
    
  
  

• For erythromycin gluceptate


• For injection dosage forms:
  
  • For treatment of infections:
    
    • Adults and teenagers—250 to 500 milligrams (mg) injected into a vein every six hours; or 3.75 to 5 mg per kilogram (kg) (1.7 to 2.3 mg per pound) of body weight injected into a vein every six hours.
    
    
    • Children—Dose is based on body weight. The usual dose is 3.75 to 5 mg per kg (1.7 to 2.3 mg per pound) of body weight injected into a vein every six hours.
    
    
  
  

• For erythromycin lactobionate


• For injection dosage forms:
  
  • For treatment of infections:
    
    • Adults and teenagers—250 to 500 milligrams (mg) injected into a vein every six hours; or 3.75 to 5 mg per kilogram (kg) (1.7 to 2.3 mg per pound) of body weight injected into a vein every six hours.
    
    
    • Children—Dose is based on body weight. The usual dose is 3.75 to 5 mg per kg (1.7 to 2.3 mg per pound) of body weight injected into a vein every six hours.
    
    
  
  

• For erythromycin stearate


• For oral dosage forms (oral suspension, tablets):
  
  • For treatment of infections:
    
    • Adults and teenagers—250 to 500 milligrams (mg) two to four times a day.
    
    
    • Children—Dose is based on body weight. The usual dose is 7.5 to 12.5 mg per kilogram (kg) (3.4 to 5.6 mg per pound) of body weight four times a day; or 15 to 25 mg per kg (6.8 to 11.4 mg per pound) of body weight two times a day.
    
    
  
  
  • For prevention of heart infections:
    
    • Adults and teenagers—Take 1 gram two hours before your dental appointment or surgery, then 500 mg six hours after taking the first dose.
    
    
    • Children—Dose is based on body weight. The usual dose is 20 mg per kg (9.1 mg per pound) of body weight two hours before the dental appointment or surgery, then 10 mg per kg (4.5 mg per pound) of body weight six hours after taking the first dose.
    
    
  
  

Missed Dose

If you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Keep out of the reach of children.

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Do not keep outdated medicine or medicine no longer needed.

Precautions While Using Erythrocin Stearate

If your symptoms do not improve within a few days, or if they become worse, check with your doctor.

Erythrocin Stearate Side Effects

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

Less common

• Fever


• nausea


• skin rash, redness, or itching


• stomach pain (severe)


• unusual tiredness or weakness


• vomiting


• yellow eyes or skin–with erythromycin estolate (rare with other erythromycins)

Less common - with erythromycin injection only

• Pain, swelling, or redness at place of injection

Rare

• Fainting (repeated)


• irregular or slow heartbeat


• loss of hearing (temporary)

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common

• Abdominal or stomach cramping and discomfort


• diarrhea


• nausea or vomiting

Less common

• Sore mouth or tongue


• vaginal itching and discharge

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

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Erythromycin Ointment

Pronunciation: eh-RITH-roe-MYE-sin
Generic Name: Erythromycin
Brand Name: Akne-Mycin

Erythromycin Ointment is used for:

Treating severe acne. It may also be used for other conditions as determined by your doctor.

Erythromycin Ointment is a topical macrolide antibiotic that is thought to improve acne by slowing the growth of bacteria on the skin, which causes acne.

Do NOT use Erythromycin Ointment if:

• you are allergic to any ingredient in Erythromycin Ointment

Contact your doctor or health care provider right away if any of these apply to you.

Before using Erythromycin Ointment:

Some medical conditions may interact with Erythromycin Ointment. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:

• if you are pregnant, planning to become pregnant, or are breast-feeding


• if you are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement


• if you have allergies to medicines, food, or other substances


• if you have liver disease or you have a blood disorder called porphyria

Some MEDICINES MAY INTERACT with Erythromycin Ointment. Tell your health care provider if you are taking any other medicines, especially any of the following:

• Efavirenz or rifampin because they may decrease Erythromycin Ointment's effectiveness


• Arsenic, cimetidine,diltiazem,dofetilide,HIV protease inhibitors (eg, ritonavir), imidazoles (eg, ketoconazole), pimozide, QT-prolonging agents (eg, quinidine, sotalol), quinolones (eg, ciprofloxacin), streptogramins (eg, quinupristin/dalfopristin), or verapamil because side effects, such as heart toxicity or irregular heartbeat, may occur


• Anticoagulants (eg, warfarin), aldosterone blockers (eg, spironolactone), alfentanil, arsenic, astemizole, benzodiazepines (eg, alprazolam), bromocriptine, buspirone, carbamazepine, cilostazol, cisapride, clozapine, corticosteroids (eg, hydrocortisone), cyclosporine, digitoxin, digoxin, disopyramide, ergot alkaloids (eg, ergotamine , felodipine, H₁ antagonists (eg, diphenhydramine), HMG-CoA reductase inhibitors (eg, simvastatin), imatinib, macrolide immunosuppressants (eg, tacrolimus), meglitinide antidiabetics (eg, repaglinide), midazolam, phosphodiesterase type 5 inhibitors (eg, sildenafil), pimozide, QT-prolonging agents (eg, quinidine, sotalol), quinolones (eg, ciprofloxacin, rifampin, serotonin reuptake inhibitors (eg, fluoxetine), sumatriptan theophyllines, tricyclic antidepressants (eg, amitriptyline), valproic acid, or vinca alkaloids (eg, vincristine) because the risk of their side effects may be increased by Erythromycin Ointment

This may not be a complete list of all interactions that may occur. Ask your health care provider if Erythromycin Ointment may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.

How to use Erythromycin Ointment:

Use Erythromycin Ointment as directed by your doctor. Check the label on the medicine for exact dosing instructions. Check the label on the medicine for exact dosing instructions.

• Wash affected areas with soap and water. Rinse well and pat dry before applying the medicine. Moisten a pad or use your fingertips to apply the medicine. Cover the affected and surrounding areas with a thin film of medicine. Wash your hands after you finish using Erythromycin Ointment.


• Erythromycin Ointment works best if it is used at the same time each day.


• To clear up your infection completely, take Erythromycin Ointment for the full course of treatment. Keep taking it even if you feel better in a few days.


• If you miss a dose of Erythromycin Ointment, take it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not take 2 doses at once.

Ask your health care provider any questions you may have about how to use Erythromycin Ointment.

Important safety information:

• Erythromycin Ointment is for external use only. Avoid contact with the eyes, nose, mouth, and other mucous membranes. If you get Erythromycin Ointment in your eyes, immediately rinse them out with cool tap water.


• If severe diarrhea or stomach pain or cramping develops during treatment or within several months after treatment with Erythromycin Ointment, check with your doctor or pharmacist right away. Do not treat it without first checking with your doctor.


• Be sure to use Erythromycin Ointment for the full course of treatment. If you do not, the medicine may not clear up your infection completely. The bacteria could also become less sensitive to this or other medicines. This could make the infection harder to treat in the future.


• Long-term or repeated use of Erythromycin Ointment may cause a second infection. Tell your doctor if signs of a second infection occur. Your medicine may need to be changed to treat this.


• PREGNANCY and BREAST-FEEDING: If you become pregnant, contact your doctor. You will need to discuss the benefits and risks of using Erythromycin Ointment while you are pregnant. Erythromycin Ointment is found in breast milk. If you are or will be breast-feeding while you use Erythromycin Ointment, check with your doctor. Discuss any possible risks to your baby.

Possible side effects of Erythromycin Ointment:

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome:

Peeling; redness; skin irritation.

Seek medical attention right away if any of these SEVERE side effects occur:

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); bloody stools; diarrhea; stomach cramps/pain.

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.

If OVERDOSE is suspected:

Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately. Erythromycin Ointment may be harmful if swallowed.

Proper storage of Erythromycin Ointment:

Store Erythromycin Ointment at room temperature, between 68 and 77 degrees F (20 and 25 degrees C), in a tightly-closed container. Store away from heat and light. Keep Erythromycin Ointment out of the reach of children and away from pets.

General information:

• If you have any questions about Erythromycin Ointment, please talk with your doctor, pharmacist, or other health care provider.


• Erythromycin Ointment is to be used only by the patient for whom it is prescribed. Do not share it with other people.


• If your symptoms do not improve or if they become worse, check with your doctor.


• Check with your pharmacist about how to dispose of unused medicine.

This information is a summary only. It does not contain all information about Erythromycin Ointment. If you have questions about the medicine you are taking or would like more information, check with your doctor, pharmacist, or other health care provider.

Issue Date: February 1, 2012

Database Edition 12.1.1.002

Copyright © 2012 Wolters Kluwer Health, Inc.

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