Cinryze

c1 esterase inhibitor (human)

Dosage Form: injection, powder, lyophilized, for solution
FULL PRESCRIBING INFORMATION

Cinryze™ (C1 Esterase Inhibitor [Human])

Freeze dried powder

Indications and Usage for Cinryze

Cinryze is a C1 esterase inhibitor indicated for routine prophylaxis against angioedema attacks in adolescent and adult patients with Hereditary Angioedema (HAE).

Cinryze Dosage and Administration

For Intravenous Use, Freeze-Dried powder for Reconstitution.

Routine prophylaxis against HAE Attacks

• A dose of 1,000 Units Cinryze can be administered every 3 or 4 days for routine prophylaxis against angioedema attacks in HAE patients.


• Cinryze is administered at an injection rate of 1 mL per minute.

Table 1 Routine Prophylaxis Dosing

Indication	Dose	Initial Infusion rate	Maintenance infusion rate (if tolerated)
Routine prophylaxis against HAE attacks	1,000 Units Intravenous every 3 or 4 days	1 mL/min (10 min)	1 mL/min (10 min)

Instructions for Use

The procedures below are provided as general guidelines for the reconstitution and administration of Cinryze. Use either the Mix2Vial® transfer device or a commercially available double-ended needle.

Cinryze IS A LYOPHILIZED POWDER THAT IS SUPPLIED IN A VACUUM-SEALED VIAL.

Always work on a clean surface and wash your hands before performing the following procedures.

Reconstitution, product administration, and handling of the administration set and needles must be done with caution. Percutaneous puncture with a needle contaminated with blood can transmit infectious viruses including HIV (AIDS) and hepatitis. Obtain immediate medical attention if injury occurs. Place needles in a sharps container after single use. Discard all equipment, including any reconstituted Cinryze in an appropriate container.

Preparation and Handling

• Prior to reconstitution, Cinryze should be protected from light.


• Cinryze should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. The reconstituted solution should be colorless to slightly blue, and free from visible particles. Do not use if turbid or discolored.


• The Cinryze vial is for single use only. Cinryze contains no preservative. Any vial that has been entered should be used promptly. Partially used vials should be discarded in accordance with biohazard procedures.


• Do not mix Cinryze with other materials.


• Do not use if frozen.


• Do not use after expiration date.

Reconstitution:

Two vials of reconstituted Cinryze are combined for a single dose. Sterile Water for Injection, USP, is required and not supplied with Cinryze.

1. Aseptic technique should be used during the reconstitution procedure.


2. Bring the Cinryze (powder) and Sterile Water for Injection, USP (diluent) (not supplied) to room temperature if refrigerated.


3. Remove caps from the Cinryze and diluent vials.


4. Cleanse stoppers with an alcohol wipe or swab, and allow them to dry prior to use.


5. Remove protective covering from the top of the Mix2Vial transfer device package. Do not remove the device from the package.


6. Note: Diluent vial must be accessed prior to Cinryze vial to prevent loss of vacuum. Place diluent on a flat surface and insert the blue end of the device into the diluent vial, pushing down until the spike penetrates through the center of the diluent vial stopper and the device snaps in place (Figure 1). The Mix2Vial transfer device must be positioned completely vertical prior to penetrating the stopper closure.


7. Remove the plastic package and discard it (Figure 2). Take care not to touch the exposed end of the device.


8. Place vial of Cinryze on a flat surface. Invert diluent vial containing 5 mL Sterile Water for Injection, USP, and insert the clear end into the Cinryze vial, pushing down until the spike penetrates the rubber stopper and the device snaps into place. The Mix2Vial transfer device must be positioned completely vertical prior to penetrating the stopper closure. The Sterile Water for Injection, USP will automatically flow into the vial of Cinryze (Figure 3), because the vacuum in the vial will draw in the diluent. If there is no vacuum in the vial, do not use the product.


9. Gently swirl (do not shake) the Cinryze vial until all powder is dissolved. Be sure that Cinryze is completely dissolved (Figure 4). Disconnect the Sterile Water for Injection, USP vial by turning it counterclockwise (Figure 5). Do not remove the clear end of the Mix2Vial transfer device from the vial of Cinryze.

One vial of reconstituted Cinryze contains 5 mL of C1 esterase inhibitor at a concentration of 100 Units/mL. Reconstitute two vials of Cinryze for one dose. Repeat steps 1 to 9 above using an additional package containing a Mix2Vial transfer device to reconstitute the second of two vials of Cinryze. Do not reuse the Mix2Vial transfer device.

Administration

Two vials of reconstituted Cinryze are combined for a single dose.

1. Use Aseptic Technique.


2. After reconstitution, the solutions are colorless to slightly blue and clear. Do not use the product if the solutions are turbid or discolored.


3. Cinryze must be administered at room temperature within 3 hours after reconstitution.


4. Please refer to the illustrations in steps 7 to 9 included within the Patient Information Leaflet. Utilizing a sterile, disposable 10 mL syringe, draw back the plunger to admit 5 mL air into the syringe.


5. Attach the syringe onto the top of the clear end of the Mix2Vial transfer device by turning it clockwise.


6. Invert the vial and inject air into the solution and then slowly withdraw the reconstituted Cinryze into the syringe.


7. Detach the syringe from the vial by turning it counterclockwise and releasing it from the clear end of the Mix2Vial transfer device.


8. Using the same syringe, repeat steps 4 to 7 with a second vial of Cinryze to make the complete dose.


9. Attach a suitable needle or infusion set with winged adapter, and inject intravenously. As a guideline, administer 1,000 Units (reconstituted in 10 mL) of Cinryze by intravenous injection at a rate of 1 mL per minute over 10 minutes. (see Clinical Studies, [14]) Please refer to the illustration in step 3 of the self administration section within the Patient Information Leaflet.


10. Dispose of all unused solution, the empty vial(s), and the used needles and syringes in an appropriate container for throwing away waste that might hurt others if not handled properly.

3. DOSAGE FORMS AND STRENGTHS

• Cinryze is a lyophilized preparation available in a single-use vial that contains 500 Units (U) human C1 esterase inhibitor.


• Each vial must be reconstituted with 5 mL Sterile Water for Injection, USP (diluent) (not supplied).


• Two reconstituted vials must be used to make a single, 1,000 Units, dose.

Contraindications

Cinryze is contraindicated in patients who have manifested life-threatening immediate hypersensitivity reactions, including anaphylaxis to the product.

Warnings and Precautions

Sensitivity

Severe hypersensitivity reactions may occur. The signs and symptoms of hypersensitivity reactions may include the appearance of hives, urticaria, tightness of the chest, wheezing, hypotension and/or anaphylaxis experienced during or after injection of Cinryze.

Because hypersensitivity reactions may have symptoms similar to HAE attacks, treatment methods should be carefully considered.

In case of hypersensitivity, Cinryze infusion should be discontinued and appropriate treatment instituted. Epinephrine should be immediately available for treatment of acute severe hypersensitivity reaction. (See Patient Counseling Information [17])

Thrombotic Events

Thrombotic events have been reported in association with C1 esterase inhibitor products when used off-label at high doses.2 Animal studies have supported a concern about the risk of thrombosis from intravenous administration of C1 esterase inhibitor products. 3 (see Sections 10 OVERDOSAGE and 13.2 Animal Toxicology and/or Pharmacology)

In an open label trial further investigating the use of Cinryze for prevention (n=146) of HAE attacks, 5 serious thrombotic events (including myocardial infarction, deep vein thrombosis, pulmonary embolism and 2 events of cerebrovascular accident) occurred. Subjects had underlying risk factors for thrombotic events. Patients with known risk factors for thrombotic events should be monitored closely while taking Cinryze.

Transmissible Infectious Agents

Because Cinryze is made from human blood, it may carry a risk of transmitting infectious agents, e.g. viruses, and, theoretically, the Creutzfeldt-Jakob (CJD) agent [11]. ALL infections thought by a physician possibly to have been transmitted by Cinryze should be reported by the physician or other healthcare provider to ViroPharma Biologics, Inc. [(877) 945-1000]. The physician should discuss the risks and benefits of this product with the patient, before prescribing or administering it to the patient. (See Patient Counseling Information [17])

Adverse Reactions

The most serious adverse events observed in clinical studies of Cinryze have been death due to non-catheter related foreign body embolus, pre-eclampsia resulting in emergency C-section, stroke, and exacerbation of HAE attacks, none of which have been considered drug related.

The most common drug related adverse reactions observed at a rate ≥ 5% were upper respiratory tract infection, sinusitis, rash, and headache.

Clinical Trials Experience

Because clinical studies 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.

Routine Prophylaxis

Twenty-four subjects were evaluated in study LEVP2005-1/B for routine prophylaxis.

There were no treatment-emergent serious adverse reactions in study LEVP2005-1/B.

Adverse reactions in trial LEVP2005-1/B that occurred in at least two subjects during Cinryze prophylaxis, irrespective of the causality assessment, are given in the following table:

Table 2 Adverse Reactions in Routine Prophylaxis Study LEVP2005-1/B Irrespective of Causality

Adverse Reaction	Number of Adverse Events	Number of Subjects (N = 24)
Sinusitis	8	5
Rash	7	5
Headache	4	4
Upper respiratory tract infection	3	3
Viral upper respiratory tract infection	5	3
Bronchitis	2	2
Limb injury	2	2
Back pain	2	2
Pain in extremity	2	2
Pruritus	2	2

More than 9000 doses of Cinryze have been administered to over 180 patients in all controlled and open label clinical studies. All patients were evaluated and found negative for seroconversion to parvovirus B19, Hepatitis B, Hepatitis C and HIV.

No clinically relevant antibody formation was seen in clinical trials of prophylaxis.

Postmarketing Experience

Because postmarketing reporting of adverse reactions is voluntary and from a population of uncertain size, it is not always possible to reliably estimate the frequency of these reactions or establish a causal relationship to product exposure.

Postmarketing adverse reactions include local infusion site reactions (including pain, rash, erythema, inflammation or hematoma at the infusion site).

Postmarketing thrombotic events have been reported, including catheter-related and deep venous thromboses, transient ischemic attack, and stroke. Patients with known risk factors for thrombotic events should be monitored closely. (See Section 5.2 Thrombotic events in WARNINGS AND PRECAUTIONS)

Drug Interactions

No drug interaction studies have been conducted.

USE IN SPECIFIC POPULATIONS

Pregnancy

Pregnancy Category C. No animal data are available. No adequate and well-controlled studies were conducted in pregnant women. It is not known whether Cinryze can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Cinryze should be given to a pregnant woman only if clearly needed.

Labor and Delivery

The safety and effectiveness of Cinryze administration prior to or during labor and delivery have not been established. Use only if clearly needed.

Nursing Mothers

It is not known whether Cinryze is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Cinryze is administered to a nursing woman.

Pediatric Use

The safety and effectiveness of Cinryze have not been established in neonates, infants, or children. Three of the 24 subjects in Study LEVP2005-1/B were under the age of 18 years (9, 14, and 16 years of age).

Geriatric Use

The clinical study LEVP2005-1/B did not include sufficient numbers of subjects 65 years of age and older to determine whether they respond differently from younger subjects.

Overdosage

The maximum dose administered in clinical studies was 4000 Units given over approximately 5 hours (an average dose of 57 Units/kg) and 9000 Units given over a 7 day period. There have been no overdosages of Cinryze reported during clinical studies.

In vitro and in vivo animal thrombogenicity studies with Cinryze showed a potential for clot formation when Cinryze was administered at doses 14 times the recommended clinical dose (greater than 200U/kg). Thrombotic events have been reported in association with C1 esterase inhibitor products when used off-label at high doses.2 Animal studies have supported a concern about the risk of thrombosis from intravenous administration of C1 esterase inhibitor products.3 (see Section 13.2 Animal Toxicology and/or Pharmacology and Section 5.2 Thrombotic events in WARNINGS AND PRECAUTIONS).

Cinryze Description

Cinryze (C1 esterase inhibitor [human]) is a sterile, stable, lyophilized preparation of C1 esterase inhibitor derived from human plasma. Cinryze is manufactured from human plasma purified by a combination of filtration and chromatographic procedures. The specific activity of Cinryze is 4.0 – 9.0 units/mg protein. The purity is ≥ 90% human C1 esterase inhibitor. Following reconstitution with 5 mL of Sterile Water for Injection, USP, each vial contains approximately 500 units of functionally active C1 esterase inhibitor, pH 6.6 - 7.4, and an osmolality between 200 – 400 mosmol/kg. One Unit (U) of Cinryze corresponds to the mean quantity of C1 esterase inhibitor present in 1 mL of normal fresh plasma.

Cinryze, when reconstituted with 5 mL of Sterile Water for Injection, USP contains the following excipients: 4.1 mg/mL sodium chloride, 21 mg/mL sucrose, 2.6 mg/mL trisodium citrate, 2.0 mg/mL L-Valine, 1.2 mg/mL L-Alanine, and 4.5 mg/mL L-Threonine.

The following manufacturing steps are designed to reduce the risk of viral transmission:

• Screening donors at U.S. licensed blood collection centers to rule out infection with Human Immunodeficiency Virus (HIV-1/HIV-2), Hepatitis B Virus, or Hepatitis C Virus.


• Testing plasma pools by in-process NAT for parvovirus B19 via minipool testing and the limit of B19 in the manufacturing pool is set not to exceed 104 IU of B19 DNA per mL.


• Use of two independent viral reduction steps in the manufacture of Cinryze: pasteurization (heat treatment at 60°C for 10 hours in solution with stabilizers) and nanofiltration through two sequential 15 nm filters.

These viral reduction steps, along with a step in the manufacturing process, PEG precipitation, have been validated in a series of in vitro experiments for their capacity to inactivate/remove a wide range of viruses of diverse physicochemical characteristics including: Human Immunodeficiency Virus (HIV), Hepatitis A Virus (HAV), and the following model viruses: Bovine Viral Diarrhea Virus (BVDV) as a model virus for HCV, Canine Parvovirus (CPV) as a model virus for Parvovirus B19, Pseudorabies Virus (PRV) as a model virus for large enveloped DNA viruses (e.g. herpes virus). Total mean log10 reductions are shown in Table 3.

Table 3 Log10 Virus Reduction Factor for Selected Viruses

Process step	Log10 Virus Reduction
	Enveloped viruses			Non-enveloped viruses
	HIV	BVDV	PRV	HAV	CPV
PEG precipitation	5.1 ± 0.2	4.5 ± 0.3	6.0 ± 0.3	2.8 ± 0.2	4.2 ± 0.2
Pasteurization	> 6.1 ± 0.2	> 6.7 ± 0.3	> 6.7 ± 0.2	2.8 ± 0.3	0.1 ± 0.3
Nanofiltration	> 5.6 ± 0.2	> 5.5 ± 0.2	> 6.4 ± 0.3	> 4.9 ± 0.2	> 4.5 ± 0.3
Total reduction	> 16.8	> 16.7	> 19.1	> 10.5	> 8.7

Cinryze - Clinical Pharmacology

Mechanism of Action

C1 inhibitor is a normal constituent of human blood and is one of the serine proteinase inhibitors (serpins). The primary function of C1 inhibitor is to regulate the activation of the complement and intrinsic coagulation (contact system) pathway. C1 inhibitor also regulates the fibrinolytic system. Regulation of these systems is performed through the formation of complexes between the proteinases and the inhibitor, resulting in inactivation of both and consumption of the C1 inhibitor.

HAE patients have low levels of endogenous or functional C1 inhibitor. Although the events that induce attacks of angioedema in HAE patients are not well defined, it is thought by some that increased vascular permeability and the clinical manifestation of HAE attacks are primarily mediated through contact system activation. Suppression of contact system activation by C1 inhibitor through the inactivation of plasma kallikrein and factor XIIa is thought to modulate this vascular permeability by preventing the generation of bradykinin1. Administration of Cinryze increases plasma levels of C1 inhibitor activity.

Pharmacodynamics

In clinical studies, the intravenous administration of Cinryze demonstrated an increase in plasma levels of C1 inhibitor within approximately one hour or less of administration.

Biological activity of Cinryze was shown in 35 subjects by the subsequent increase in plasma C4 levels from an average of C4 8.1 mg/mL at baseline to C4 8.6 mg/mL 12 hours after infusion of Cinryze.

Pharmacokinetics

A randomized, parallel group, open label pharmacokinetics (PK) study of Cinryze was performed in patients with non-symptomatic hereditary angioedema (HAE). The patients received either a single dose of 1,000 Units or 1,000 Units followed by a second 1,000 Units 60 minutes later. The PK results for functional C1 inhibitor are presented the following table:

Table 4 Mean pharmacokinetic parameters of Functional C1 Inhibitor

Numbers in parenthesis are number of subjects evaluated
Single dose = 1,000 Units
Double dose = 1,000 Units followed by a second 1,000 Units 60 minutes later
* One Unit is equal to the mean C1 inhibitor concentration of 1 mL of normal human plasma
Parameters	Single Dose	Double Dose
Cbaseline (units/mL)	0.31 ± 0.20 (n = 12)	0.33 ± 0.20 (n = 12)
Cmax (units/mL)	0.68 ± 0.08 (n = 12)	0.85 ± 0.12 (n = 13)
Tmax (hrs)	3.9 ± 7.3 (n = 12)	2.7 ± 1.9 (n = 13)
AUC(0-t) (units*hr/mL)	74.5 ± 30.3 (n = 12)	95.9 ± 19.6 (n = 13)
CL (mL/min)	0.85 ± 1.07 (n = 7)	1.17 ± 0.78 (n = 9)
Half-life (hours)	56 ± 36 (n = 7)	62 ± 38 (n = 9)

The maximum plasma concentrations (Cmax) and area under the plasma concentration-time curve (AUC) increased from the single to double dose, although the increase was not dose proportional. The mean half-lives of Cinryze were 56 hours (range 11 to 108 hours) for a single dose and 62 hours (range 16 to 152 hours) for the double dose.

Studies have not been conducted to evaluate the PK of Cinryze in special patient populations identified by gender, race, age (pediatric or geriatric), or the presence of renal or hepatic impairment.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

No animal studies have been completed to evaluate the effects of Cinryze on carcinogenesis, mutagenesis, and impairment of fertility.

Animal Toxicology and/or Pharmacology

Acute toxicity of Cinryze was studied in a combined acute toxicity and 7-day repeat dose/ dose range finding (DRF) study in Sprague Dawley rats. Repeat dose toxicity was studied in a 7-day repeat dose follow up to the acute dose study. The acute and repeated dose toxicity studies were performed with intravenous administration of Cinryze at dose levels of 1, 7 and 28 times normal dose. No signs of toxicity were observed in the single dose study. In the repeated dose study, no signs of toxicity were observed in the two lower doses. Repeat dosing in the rat resulted in a robust neutralizing antibody response between days 1 and 14. Therefore, toxicity in animals dosed repeatedly is difficult to interpret.

In vitro and in vivo thrombogenicity studies showed a potential for clot formation when Cinryze was administered at doses 14 times the recommended clinical dose (greater than 200U/kg).

Clinical Studies

Routine Prophylaxis Trial LEVP2005-1/B

The safety and efficacy of Cinryze prophylaxis therapy to reduce the incidence, severity, and duration of HAE attacks was demonstrated in a single randomized, double blind, placebo controlled multi-center cross-over study of 24 patients. Patients were screened to confirm a diagnosis of HAE and a history of at least two HAE attacks per month. 24 patients (mean age 38.1 years with a range of 9 to 73 years) were randomized to one of two treatment groups: either Cinryze prophylaxis for 12 weeks followed by 12 weeks of placebo prophylaxis; or randomized to placebo prophylaxis for 12 weeks followed by 12 weeks of Cinryze prophylaxis. Two subjects dropped out (one in each arm); 22 patients crossed over into period 2 and were included in the efficacy analysis. Patients were given blinded injections (Cinryze or placebo) every 3 to 4 days, approximately 2 times per week. Patients recorded all angioedema symptoms daily. An attack was defined as the subject-reported indication of swelling at any location following a report of no swelling on the previous day.

The efficacy determination was based on the number of attacks during the 12 week period while receiving Cinryze as compared to the number of attacks during the placebo treatment period. The effectiveness of C1 esterase inhibitor prophylaxis in reducing the number of HAE attacks was variable among the subjects as shown in table 5:

Table 5 LEVP2005-1/B Prevention of HAE Attacks Clinical Trial Results by Subject

Subject	Percent Reduction in Attack Frequency
1	100%
2	100%
3	100%
4	100%
5	90%
6	88%
7	84%
8	83%
9	78%
10	76%
11	60%
12	47%
13	43%
14	43%
15	32%
16	31%
17	25%
18	21%
19	10%
20	1%
21	-8%
22	-85%

Table 6 Summary Statistics on Number of HAE Attacks in LEVP2005-1/B

	Statistic	Cinryze N=22	Placebo N=22
Number of Attacks	Mean	6.1	12.7
	SD	5.4	4.8
	Median	6	13.5
	Min	0	6
	Max	17	22
GEE Analysis Results
Effect Assessed		p-value
Treatment Effect		<0.0001
Sequence Effect		0.3347
Period Effect		0.3494

Patients treated with Cinryze had a 66% reduction in days of swelling (p<0.0001), and decreases in the average severity of attacks (p=0.0006) and the average duration of attacks (p=0.0023), as shown in table 7.

Table 7 LEVP2005-1/B Clinical Trial Secondary Efficacy Outcomes

	Cinryze N=22	Placebo N=22	Treatment Effect p-value
Mean Severity of HAE Attacks (Score from 1 to 3) (SD)	1.3 (0.85)	1.9 (0.36)	0.0006
Mean Duration of HAE Attacks (Days) (SD)	2.1 (1.13)	3.4 (1.4)	0.0023
Days of Swelling (SD)	10.1 (10.73)	29.6 (16.9)	<0.0001

REFERENCES

1. Davis AE, The pathophysiology of hereditary angioedema. Clin Immunol. 2005; 114:3-9.


2. Arzneimittelkommission der Deutschen Aertzteschaft. Schwerwiegende Thrombenbildung nach Berinert HS. Dtsch Aerztebl. 2000; 97:B-864


3. Horstick, G et al, 2001. Circulation 104:3125-3131

How Supplied/Storage and Handling

• Cinryze is available in single-use vials that contain 500 Units per vial.


• Cinryze is supplied as a single glass vial of Cinryze powder to be reconstituted with 5 mL Sterile Water for Injection, USP (Not supplied).


• Cinryze, packaged for sale, is stable for 18 months when stored at 2°C–25°C (36°F-77°F).


• Do not freeze.


• Store the vial in the original carton to protect it from light.


• The reconstituted solution must be used within 3 hours of reconstitution.


• Do not use beyond the expiration date on the Cinryze vial.

Patient Counseling Information

Allergic-type Hypersensitivity Reactions

Allergic-type hypersensitivity reactions are possible [5.1]. Inform patients of the early signs of hypersensitivity reactions [including hives (itchy white elevated patches), tightness of the chest, wheezing, hypotension] and anaphylaxis. Advise patients to discontinue use of Cinryze and contact their physicians if these symptoms occur.

Pregnancy

Advise female patients to notify their physician if they become pregnant or intend to become pregnant during their routine prevention with Cinryze.

Nursing

Advise patients to notify their physician if they are breastfeeding or plan to breastfeed.

Usage While Traveling

Based on their current regimen, advise patients to bring an adequate supply of Cinryze for routine prevention when traveling. Advise patients to consult with their healthcare professional prior to travel.

Transmissible Infectious Agents

Advise patient that, because Cinryze is made from human blood, it may carry a risk of transmitting infectious agents, e.g. viruses, and, theoretically, the Creutzfeldt-Jakob (CJD) agent [5.3, 11]. The risk of transmitting disease has been reduced, but not eliminated, by carefully selecting blood donors, testing donors for infections, and inactivating or removing most viruses during the manufacturing process. Inform patients of the risks and benefits of Cinryze before prescribing or administering to the patient.

FDA-Approved Patient Labeling

Information for the Patient

Cinryze™ (SIN-rise)

(C1 Esterase Inhibitor [Human])

This leaflet summarizes important information about Cinryze. Please read it carefully before using Cinryze and each time you get a refill. There may be new information. This information does not take the place of talking with your healthcare provider, and it does not include all of the important information about Cinryze. If you have any questions after reading this, ask your healthcare provider.

Do not attempt to self-administer unless you have been taught how by your healthcare provider.

What is Cinryze?

Cinryze is an injectable medicine that is used to help prevent swelling and/or painful attacks in teenagers and adults with Hereditary Angioedema (HAE). HAE is caused by the decreased functioning of a protein called C1 esterase inhibitor, that is present in your blood and helps control inflammation (swelling) and parts of the immune system. Cinryze contains C1 esterase inhibitor. Before you can inject Cinryze into your vein (intravenous injection), you must dissolve the Cinryze powder using Sterile Water for Injection, USP. You can get supplies, including Sterile Water for Injection, USP from your pharmacist.

Who should not use Cinryze?

You should not use Cinryze if you have had life-threatening immediate hypersensitivity reactions, including anaphylaxis to the product.

What should I tell my healthcare provider before using Cinryze?

Tell your healthcare provider about all of your medical conditions, including if you

• are pregnant or planning to become pregnant. It is not known if Cinryze can harm your unborn baby.


• are breastfeeding or plan to breastfeed. It is not known if Cinryze passes into your milk and if it can harm your baby.


• have a history of blood clotting problems. Very high doses of C1 esterase inhibitor could increase the risk of blood clots.

Tell your healthcare provider and pharmacist about all of the medicines you take, including all prescription and non-prescription medicines such as over-the-counter medicines, supplements, or herbal remedies.

What are the possible side effects of Cinryze?

Allergic reactions may occur with Cinryze. Call your healthcare provider or get emergency support services right away if you have any of the following symptoms:

• wheezing


• difficulty breathing


• chest tightness


• turning blue (look at lips and gums)


• fast heartbeat


• swelling of the face


• faintness


• rash


• hives

In clinical studies, the most common side effects seen with Cinryze were upper respiratory tract infection, sinusitis, rash, and headache.

These are not all the possible side effects of Cinryze.

Tell your healthcare provider about any side effect that bothers you or that does not go away. You can also report side effects to the FDA at 1-800-FDA-1088.

You can ask your healthcare provider for information that is written for healthcare providers.

How should I store Cinryze?

Do not freeze Cinryze.

Store Cinryze in a refrigerator or at room temperature between 36° to 77°F (2° to 25°C).

Keep Cinryze in the original carton to protect it from light.

Do not use Cinryze after the expiration date on the vial.

After preparing Cinryze, you can store it at room temperature for up to 3 hours. If you have not used it within 3 hours, throw it away.

Only use the dissolved Cinryze if it is colorless to slightly blue, clear and free from visible particles.

What else should I know about Cinryze?

Medicines are sometimes prescribed for purposes other than those listed here. Do not use Cinryze for a condition for which it is not prescribed. Do not share Cinryze with other people, even if they have the same symptoms that you have.

Because Cinryze is made from human blood, it may carry a risk of transmitting infectious agents, e.g. viruses, and, theoretically, the Creutzfeldt-Jakob (CJD) agent.

This leaflet summarizes the most important information about Cinryze. If you would like more information, talk to your healthcare provider. You can ask your healthcare provider or pharmacist for information about Cinryze that was written for healthcare professionals.

Instructions for Use

Do not attempt to self-administer unless you have been taught how by your healthcare provider.

See the step-by-step instructions for injecting Cinryze at the end of this leaflet. You should always follow the specific instructions given by your healthcare provider. The steps listed below are general guidelines for using Cinryze. If you are unsure of the steps, please call your healthcare provider or pharmacist before using.

Call your healthcare provider right away if swelling is not controlled after using Cinryze.

Your healthcare provider will prescribe the dose that you should take.

Call your healthcare provider if you take too much Cinryze.

Call your healthcare provider if you miss a dose of Cinryze.

Talk to your healthcare provider before traveling. You should plan to bring enough Cinryze for your treatment during this time.

Preparation of Cinryze

Always wash your hands before doing the following steps. Try to keep everything clean and germ-free while you are reconstituting Cinryze. Once you open the vials, you should finish preparing Cinryze as soon as possible. This will help to keep them germ-free.

Cinryze IS A FREEZE-DRIED POWDER THAT IS SUPPLIED IN A VACUUM-SEALED VIAL.

Note: Two vials of Cinryze are required for each dose. You should reconstitute both vials according to steps 1 through 6.

1. Let the vial of Cinryze and the vial of Sterile Water for Injection, USP (diluent) reach room temperature.


2. Remove the cap from the Cinryze vial and Sterile Water for Injection, USP (diluent) vial to show the center part of the rubber stopper.
   
   
   


3. Wipe the top of each vial with an alcohol wipe or swab, and allow it to dry. Do not blow on the stopper to dry it faster. Place each vial on a flat surface. After cleaning, do not touch the rubber stopper with your hand or allow it to touch any surface.
   
   
   


4. Note: Diluent vial must be penetrated before the Cinryze vial to prevent loss of vacuum. Remove the protective covering from the top of the Mix2Vial transfer device package. Do not remove the device from the pack

Charcoal Plus DS

Generic Name: charcoal (CHAR coal)

Brand Names: Actidose-Aqua, Activated Charcoal, Charcoal Plus DS, EZChar, Insta-Char, Liqui-Char, Optimum Charcoal

What is Charcoal Plus DS (charcoal)?

Charcoal is used to treat stomach pain caused by excess gas, diarrhea, or indigestion.

Charcoal also is used to relieve itching related to kidney dialysis treatment and to treat poisoning or drug overdose.

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

What is the most important information I should know about Charcoal Plus DS (charcoal)?

You should not use this medication if you have ever had an allergic reaction to charcoal.

Before taking this medication, tell your doctor if you are allergic to any drugs, or if you have liver or kidney disease, or any type of serious illness.

In a poisoning or overdose situation, it may not be possible before you are treated to tell your caregivers about any health conditions you have or if you are pregnant or breast-feeding. However, make sure any doctor caring for you afterward knows that you have received this medication.

If you are taking charcoal at home to treat diarrhea, stop taking it and call your doctor if your diarrhea lasts longer than 2 days or you also have a fever. Do not take charcoal with any other medicine. Take your dose of charcoal at least 2 hours before or 1 hour after a dose of any other medicine. Charcoal binds to other drugs and can make them less effective, which could become dangerous.

What should I discuss with my healthcare provider before taking Charcoal Plus DS (charcoal)?

You should not use this medication if you have ever had an allergic reaction to charcoal.

If possible, before you receive charcoal, tell your doctor if you are allergic to any drugs, or if you have:

• 
  

  liver disease;

  
  


• 
  

  kidney disease; or

  
  


• 
  

  any type of serious illness.

  
  

If you have any of these conditions, you may need a dose adjustment or special tests to safely take this medication.

It is not known whether charcoal is harmful to an unborn baby. Before you take charcoal, tell your doctor if you are pregnant or plan to become pregnant during treatment. It is not known whether charcoal 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.

In a poisoning or overdose situation, it may not be possible to tell your caregivers that you are pregnant or breast-feeding before you are treated with charcoal. However, make sure any doctor caring for your pregnancy or your baby knows that you have received the medication.

Do not give this medication to a child younger than 1 year old without the advice of a doctor.

How should I take Charcoal Plus DS (charcoal)?

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

Take this medicine with a full glass (8 ounces) of water. Do not crush, break, or chew a charcoal tablet or capsule. Swallow the pill whole.

Charcoal is usually taken after meals or at the first sign of stomach discomfort.

Stop taking charcoal and call your doctor if your diarrhea lasts longer than 2 days or you also have a fever.

Store charcoal at room temperature away from moisture and heat.

What happens if I miss a dose?

Since charcoal is often taken only when needed, you may not be on a dosing schedule. If you are taking the medication regularly, take the missed dose as soon as you remember. If it is almost time for your next dose, wait until then to take the medicine and skip the missed dose. Do not take extra medicine to make up the missed dose.

What happens if I overdose?

Seek emergency medical attention if you think you have used too much of this medicine.

An overdose of charcoal is not likely to cause life-threatening symptoms.

What should I avoid while taking Charcoal Plus DS (charcoal)?

Do not take charcoal with any other medicine. Take your dose of charcoal at least 2 hours before or 1 hour after a dose of any other medicine. Charcoal binds to other drugs and can make them less effective, which could become dangerous.

Charcoal Plus DS (charcoal) side effects

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

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 Charcoal Plus DS (charcoal)?

There may be other drugs that can interact with charcoal. Tell your doctor about all your prescription and over-the-counter medications, vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start a new medication without telling your doctor.

More Charcoal Plus DS resources

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

• Charcoal Natural MedFacts for Professionals (Wolters Kluwer)


• Charcoal MedFacts Consumer Leaflet (Wolters Kluwer)


• Actidose-Aqua Suspension MedFacts Consumer Leaflet (Wolters Kluwer)


• Charcoal, Activated Monograph (AHFS DI)

Compare Charcoal Plus DS with other medications

• Gas
• Gastrointestinal Decontamination

Where can I get more information?

• Your pharmacist can provide more information about charcoal.

See also: Charcoal Plus DS side effects (in more detail)

Cleocin T Swab

Pronunciation: KLIN-da-MYE-sin
Generic Name: Clindamycin
Brand Name: Examples include Cleocin T and Clindets

Cleocin T Swab is used for:

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

Cleocin T Swab is a topical lincomycin antibiotic. It works by killing sensitive bacteria that cause acne and reducing the amount of free fatty acids that irritate the skin surface.

Do NOT use Cleocin T Swab if:

• you are allergic to any ingredient in Cleocin T Swab or to lincomycin


• you have Crohn disease, antibiotic-associated colitis, or ulcerative colitis

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

Before using Cleocin T Swab:

Some medical conditions may interact with Cleocin T Swab. 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, foods, or other substances


• if you have gastrointestinal (bowel) disease or diarrhea

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

• Nondepolarizing muscle relaxants (eg, vecuronium) or succinylcholine because their actions and the risk of their side effects may be increased by Cleocin T Swab


• Erythromycin because it may decrease Cleocin T Swab's effectiveness

This may not be a complete list of all interactions that may occur. Ask your health care provider if Cleocin T Swab 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 Cleocin T Swab:

Use Cleocin T Swab as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Cleocin T Swab is for topical use on the skin only.


• Wash and completely dry the affected area.


• Remove the pledget from the jar or foil wrapper just before use. Do not use a pledget from a foil wrapper that has a broken seal. With pledget, gently apply a thin film of medicine. You may use more than 1 pledget if necessary to completely cover the affected area. Wash your hands immediately after using Cleocin T Swab. Throw the pledget away after using.


• Cleocin T Swab works best if it is used at the same time each day.


• Continue to use Cleocin T Swab even if your condition improves. Do not miss any doses.


• If you miss a dose of Cleocin T Swab, use 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 use 2 doses at once.

Ask your health care provider any questions you may have about how to use Cleocin T Swab.

Important safety information:

• Cleocin T Swab is for external use only. Avoid contact with the eyes because burning or irritation can occur. If contact occurs with the eyes or sensitive surfaces (eg, scraped skin, mucous membranes), wash the area with cool tap water.


• Cleocin T Swab may cause harm if it is swallowed. If you may have taken it by mouth, contact your poison control center or emergency room right away.


• Several weeks may pass before you see improvement in your acne. Continue using Cleocin T Swab for the full time recommended by your doctor.


• Be sure to use Cleocin T Swab 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.


• If severe diarrhea, stomach pain or cramping, or bloody stools develop during treatment or within several months after treatment with Cleocin T Swab, check with your doctor or pharmacist right away. Do not treat it without first checking with your doctor.


• Cleocin T Swab should be used with extreme caution in CHILDREN younger than 12 years old; safety and effectiveness in these children have not been confirmed.


• PREGNANCY and BREAST-FEEDING: If you become pregnant, contact your doctor. You will need to discuss the benefits and risks of using Cleocin T Swab while you are pregnant. It is not known if Cleocin T Swab is found in breast milk. Do not breast-feed while using Cleocin T Swab.

Possible side effects of Cleocin T Swab:

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:

Dry skin; mild stinging after applying.

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); blood or mucus in stools; diarrhea; stomach pain; swelling, redness, burning, or peeling of the skin.

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.

See also: Cleocin T side effects (in more detail)

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. Cleocin T Swab may be harmful if swallowed.

Proper storage of Cleocin T Swab:

Store Cleocin T Swab at room temperature, between 68 to 77 degrees F (20 to 25 degrees C), in a tightly closed container. Store away from heat, moisture, and light. Do not store in the bathroom. Keep Cleocin T Swab out of the reach of children and away from pets.

General information:

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


• Cleocin T Swab 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 Cleocin T Swab. 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.

More Cleocin T resources

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

Compare Cleocin T with other medications

• Acne
• Perioral Dermatitis

Ciloxan eent

Generic Name: Ciprofloxacin Hydrochloride eent
Class: Antibacterials
Molecular Formula: C₁₇H₁₈FN₃O₃•ClH•H₂O
CAS Number: 86393-32-0

Introduction

Fluoroquinolone antibacterial.^{1 2 5 6 8}

Uses for Ciloxan

Bacterial Ophthalmic Infections

Ophthalmic ointment: Treatment of conjunctivitis caused by susceptible strains of Staphylococcus aureus, S. epidermidis, Streptococcus pneumoniae, Haemophilus influenzae, or viridans streptococci.¹¹⁹

Ophthalmic solution: Treatment of conjunctivitis caused by susceptible strains of S. aureus, S. epidermidis, S. pneumoniae, or H. influenzae.¹

Some clinicians suggest that quinolones be reserved principally for severe bacterial conjunctivitis because of potential development of quinolone resistance, and possibly, cost considerations.^{4 111 116}

Ophthalmic solution: Treatment of keratitis (corneal ulcer) caused by susceptible strains of Pseudomonas aeruginosa, Serratia marcescens, S. aureus , S. epidermidis, S. pneumoniae, or viridans streptococci.^{1 24 25 26 27 101 102 103 112}

Some clinicians suggest that single-agent topical fluoroquinolone therapy be considered for initial treatment in patients with equivocal gram stain results on diagnostic corneal smear, presence of >1 organism, contact lens associated keratitis (suspected to be caused by gram-negative bacteria), or in settings where culture and sensitivity tests are impossible or impractical.¹¹⁸

Bacterial Otic Infections

Ciprofloxacin-dexamethasone otic suspension: Treatment of acute otitis externa caused by susceptible strains of S. aureus or Ps. aeruginosa.¹²⁵

Ciprofloxacin-hydrocortisone otic suspension: Treatment of acute otitis externa caused by susceptible strains of S. aureus, Ps. aeruginosa, or Proteus mirabilis.¹²⁰

Ciprofloxacin-dexamethasone otic suspension: Treatment of acute otitis media caused by susceptible strains of S. aureus, S. pneumoniae, H. influenzae, Moraxella catarrhalis, or Ps. aeruginosa in patients with tympanostomy tubes.¹²⁵

Ciloxan Dosage and Administration

General

• 
  

  Avoid contamination of container.^{1 116 119 120 125}

  
  

Administration

Ophthalmic Administration

Apply topically to the eye as an ophthalmic ointment or solution.^{1 116 119}

Not for injection.^{1 119}

Remove contact lenses before administration of ophthalmic solution.¹

For treatment of bacterial keratitis, administer ophthalmic solution around the clock.^{25 115}

Otic Administration

Administered as otic suspension in fixed combination with dexamethasone or hydrocortisone.^{120 125}

For otic use only.^{120 125} Not for ophthalmic use.^{120 125} Not for injection.^{120 125}

Discard unused portion after therapy is completed.^{120 125}

Prior to administration, warm container in hand for 1–2 minutes before use to avoid dizziness associated with instillation of cold solution into ear canal.^{120 125} Shake well before use.^{120 125}

To administer fixed combination otic suspensions of ciprofloxacin with dexamethasone or hydrocortisone for treatment of acute otitis externa, instill drops while patient lies with affected ear upward; maintain position for 30–60 seconds to facilitate penetration of drops into ear.^{120 125} Repeat for opposite ear if necessary.^{120 125}

To administer ciprofloxacin-dexamethasone otic suspension for treatment of acute otitis media in pediatric patients with tympanostomy tubes, instill drops while patient lies with affected ear upward.¹²⁵ Pump tragus 5 times by pushing inward to facilitate penetration of drops into middle ear; maintain position for 60 seconds.¹²⁵ Repeat for opposite ear if necessary.¹²⁵

Dosage

Available as ciprofloxacin hydrochloride; dosage expressed in terms of ciprofloxacin.^{1 108 119 120 125}

Pediatric Patients

Ophthalmic Infections

Conjunctivitis (S. aureus, S. epidermidis, S. pneumoniae, H. influenzae, or viridans streptococci)

Ophthalmic

Ointment: In children ≥2 years of age, apply approximately 1.27 cm (½ inch) ribbon into conjunctival sac of affected eye(s) 3 times daily for 2 days, then twice daily for next 5 days.¹¹⁹

Conjunctivitis (S. aureus, S. epidermidis, S. pneumoniae, or H. influenzae)

Ophthalmic

Solution: In children ≥1 year of age, 1 or 2 drops of 0.3% solution into conjunctival sac of affected eye(s) every 2 hours while awake for 2 days, then 1–2 drops every 4 hours while awake for next 5 days.^{1 3}

Keratitis

Ophthalmic

Solution: In children ≥1 year of age, 2 drops of 0.3% solution into affected eye(s) every 15 minutes for 6 hours, followed by 2 drops every 30 minutes for remainder of first day.^{1 3 25} On the second day, instill 2 drops into affected eye(s) every hour, and on days 3–14, instill 2 drops every 4 hours.^{1 3} May continue longer than 14 days if corneal reepithelialization is not complete.^{1 3}

Otic Infections

Otitis Externa (S. aureus or Ps. aeruginosa)

Otic

Ciprofloxacin-dexamethasone otic suspension: In children ≥6 months of age, 4 drops into canal of affected ear(s) twice daily for 7 days.¹²⁵

Otitis Externa (S. aureus, Ps. aeruginosa, or P. mirabilis)

Otic

Ciprofloxacin-hydrocortisone otic suspension: In children ≥1 year of age, 3 drops into canal of affected ear(s) twice daily for 7 days.¹²⁰

Otitis Media (Acute)

Otic

Ciprofloxacin-dexamethasone otic suspension: In children ≥6 months of age, 4 drops into affected ear(s) twice daily through tympanostomy tube for 7 days.¹²⁵

Adults

Ophthalmic Infections

Conjunctivitis (S. aureus, S. epidermidis, S. pneumoniae, H. influenzae, or viridans streptococci)

Ophthalmic

Ointment: Apply approximately 1.27 cm (½ inch) ribbon into conjunctival sac of affected eye(s) 3 times daily for 2 days, then twice daily for next 5 days.¹¹⁹

Conjunctivitis (S. aureus, S. epidermidis, S. pneumoniae, or H. influenzae)

Ophthalmic

Solution: 1 or 2 drops of 0.3% solution into conjunctival sac of affected eye(s) every 2 hours while awake for 2 days, then 1–2 drops every 4 hours while awake for next 5 days.^{1 3}

Keratitis

Ophthalmic

Solution: 2 drops of 0.3% solution into affected eye(s) every 15 minutes for 6 hours, followed by 2 drops every 30 minutes for remainder of first day.^{1 3} On the second day, instill 2 drops into affected eye(s) every hour, and on days 3–14, instill 2 drops every 4 hours.^{1 3} May continue longer than 14 days if corneal reepithelialization is not complete.^{1 3}

Otic Infections

Otitis Externa (S. aureus or Ps. aeruginosa)

Otic

Ciprofloxacin-dexamethasone otic suspension: 4 drops into canal of affected ear(s) twice daily for 7 days.¹²⁵

Otitis Externa (S. aureus, Ps. aeruginosa, or P. mirabilis)

Otic

Ciprofloxacin-hydrocortisone otic suspension: 3 drops into canal of affected ear(s) twice daily for 7 days.¹²⁰

Cautions for Ciloxan

Contraindications

• 
  

  Known hypersensitivity to ciprofloxacin, other quinolones, or any ingredient in the formulation.^{1 119 120 125}

  
  


• 
  

  Otic formulations contraindicated in patients with viral infections (i.e., herpes simplex, varicella) of external ear canal.^{120 125}

  
  


• 
  

  Because commercially available ciprofloxacin-hydrocortisone fixed combination otic suspension is nonsterile, do not use if tympanic membrane is perforated.¹²⁰

  
  

Warnings/Precautions

Sensitivity Reactions

Hypersensitivity

Serious, potentially fatal hypersensitivity reactions possible, occasionally after initial systemic dose.^{1 99 119 120 125} If allergic reaction occurs, discontinue ciprofloxacin and institute appropriate therapy if indicated.^{1 119 120 125}

General Precautions

Infectious Complications.

Possible overgrowth of nonsusceptible organisms (e.g., fungi) with prolonged use; if superinfection occurs, discontinue drug and institute other appropriate therapy.^{1 119 120 125}

Patient Monitoring

Ophthalmic: Careful monitoring, including slit-lamp biomicroscopy and fluorescein staining when appropriate, may be necessary.^{1 119}

Otic: If otic infection is not improved after 1 week of treatment, obtain cultures to guide further treatment.^{120 125} If otorrhea persists after full course of therapy with ciprofloxacin-dexamethasone otic suspension, or if ≥2 episodes of otorrhea occur within 6 months, further evaluate to exclude underlying condition (e.g., cholesteatoma, foreign body, tumor).¹²⁵

Ocular Effects

In patients with bacterial keratitis, white crystalline precipitate in superficial portion of corneal defect possible; onset generally is within 1–7 days after initiation of therapy (when solution is administered repeatedly at relatively short intervals) and resolution usually during later phase of continued therapy (when administration frequency is reduced).^{1 3} Precipitate does not appear to preclude continued use nor adversely affect visual outcome or clinical course of corneal ulcer.^{1 3 25 115 116 117}

Use of Fixed Combination

When used in fixed combination with other agents, consider the cautions, precautions, and contraindications associated with the concomitant agents.

Specific Populations

Pregnancy

Category C.^{1 119 120 125}

Lactation

Distributed into milk after systemic administration; it is not known whether distributed into milk after topical application to the eye or ear.^{1 119 120 125}

Caution advised if ophthalmic solution or ointment is used in nursing women.^{1 119}

Discontinue nursing or ciprofloxacin-steroid otic suspension preparations.^{120 125}

Pediatric Use

Ophthalmic ointment: Safety and efficacy not established in children <2 years of age.¹¹⁹

Ophthalmic solution: Safety and efficacy not established in children <1 year of age.¹

Ciprofloxacin-dexamethasone otic suspension: Safety and efficacy not established in children <6 months of age, but there are no known safety concerns or differences in disease process to preclude use in children <6 months of age.¹²⁵

Ciprofloxacin-hydrocortisone otic suspension: Safety and efficacy not established in children <2 years of age, but there are no known safety concerns or differences in disease process to preclude use in children ≥1 year of age.¹²⁰

Common Adverse Effects

Ophthalmic: local burning or discomfort, lid margin crusting, crystals/scales, foreign body sensation, itching, conjunctival hyperemia, bad taste, keratopathy.^{1 119}

Otic: otic discomfort/pain/pruritus.^{120 125}

Interactions for Ciloxan

No formal drug interaction studies to date.^{1 119 125} Since systemic absorption may occur following ophthalmic or otic^{1 119 125} administration, consider possible drug interactions such as those reported with systemic administration.^{1 119 125}

Ciloxan Pharmacokinetics

Absorption

Bioavailability

Ophthalmic ointment: Extent of systemic absorption not evaluated, but mean maximal plasma ciprofloxacin concentrations expected to be <2.5 ng/mL, based on studies using 0.3% ophthalmic solution.¹¹⁹

Ophthalmic solution: Mean plasma ciprofloxacin concentrations generally averaged <2.5 ng/mL after topical application to each eye (1 drop of 0.3% ophthalmic solution every 2 hours while awake for 2 days, then every 4 hours while awake for 5 days).¹

Ciprofloxacin-dexamethasone otic suspension: Following a single bilateral 4-drop otic dose in pediatric patients after tympanostomy tube insertion, measurable plasma ciprofloxacin or dexamethasone concentrations were observed after 6 hours in 2 or 5 of 9 patients, respectively.¹²⁵ Peak plasma ciprofloxacin and dexamethasone concentrations were attained within 15 minutes to 2 hours.¹²⁵

Ciprofloxacin-hydrocortisone otic suspension: Systemic exposure to ciprofloxacin expected to be below assay quantitation limits (0.05 mg/mL) and maximum plasma hydrocortisone concentration is predicted to be within range of endogenous hydrocortisone.¹²⁰

Distribution

Extent

Distribution into human ocular tissues and fluids following topical ophthalmic or systemic administration not fully characterized to date.^{8 17}

Distributed into milk after systemic administration; it is not known whether distributed into milk after topical application to the eye or ear.^{1 119 120 125}

Stability

Storage

Ophthalmic

Ointment

2–25°C.¹¹⁹

Solution

2–25°C.¹ Protect from light.^{1 108}

Otic

Suspension

Ciprofloxacin-dexamethasone otic suspension: 15–30°C.¹²⁵ Avoid freezing; protect from light.¹²⁵

Ciprofloxacin-hydrocortisone otic suspension: <25°C.¹²⁰ Avoid freezing; protect from light.¹²⁰

Actions and SpectrumActions

• 
  

  Inhibits DNA synthesis via inhibition of type II DNA topoisomerases (DNA gyrase, topoisomerase IV).^{1 3 7 31 36 43 44 50 51 52 53 99}

  
  


• 
  

  Usually bactericidal.^{1 3 6 37 40 41 42 43 44 45 47}

  
  


• 
  

  Active in vitro against most gram-negative aerobic bacteria and many gram-positive aerobic bacteria,^{1 3 5 8 30 31 32 40 42 46 54} including penicillinase-producing, nonpenicillinase-producing, and oxacillin-resistant staphylococci;^{1 3 5 8 30 31 40 42 46 59 60} generally less active against gram-positive than gram-negative bacteria^{30 31 42 46 67 68 69} and less active in vitro on a weight basis against streptococci than against staphylococci.^{3 5 6 8 40 42 64 65 66 67 68} Most strains of Ps. cepacia, some strains of Ps. maltophilia, and most anaerobic bacteria, including Bacteroides fragilis and Clostridium difficile, are resistant.^{1 3} Inactive against fungi and viruses.^{1 3 5 6 8}

  
  

Advice to Patients

• 
  

  Importance of discontinuing drug and informing clinician at first sign of rash or other sign of hypersensitivity.^{1 99 116 119 120 125}

  
  


• 
  

  Importance of learning and adhering to proper administration techniques to avoid contamination of the product.^{1 116 119 120 125}

  
  


• 
  

  Importance of not wearing contact lenses in presence of signs and symptoms of ophthalmic bacterial infections.¹¹⁹

  
  


• 
  

  Importance of informing clinicians of existing or contemplated therapy, including prescription and OTC drugs.^{1 119 120 125}

  
  


• 
  

  Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.^{1 119 120 125}

  
  


• 
  

  Importance of informing patients of other important precautionary information. (See Cautions.)^{1 119 120 125}

  
  

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Ciprofloxacin Hydrochloride

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Ophthalmic	Ointment	0.3% (of ciprofloxacin)	Ciloxan	Alcon
	Solution	0.3% (of ciprofloxacin)	Ciloxan (with benzalkonium chloride)	Alcon
			Ciprofloxacin Ophthalmic Solution (with benzalkonium chloride)	Bausch & Lomb, Hi-Tech, Novex

Ciprofloxacin Hydrochloride Combinations

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Otic	Suspension	0.2% (of ciprofloxacin) with Hydrocortisone 1%	Cipro HC Otic Drops (with benzyl alcohol 0.9%)	Alcon
		0.3% (of ciprofloxacin) with Dexamethasone 0.1%	Ciprodex (with benzalkonium chloride)	Alcon

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 03/2011. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Ciloxan 0.3% Ointment (ALCON VISION): 3/$99.99 or 10/$267.97

Ciloxan 0.3% Solution (ALCON VISION): 5/$76.99 or 15/$210.96

Cipro HC 0.2-1% Suspension (ALCON VISION): 10/$135.99 or 30/$382.98

Ciprodex 0.3-0.1% Suspension (ALCON VISION): 7/$142.98 or 22/$407.95

Ciprofloxacin HCl 0.3% Solution (FALCON PHARMACEUTICALS): 5/$29.99 or 15/$79.96

Ciprofloxacin HCl 0.3% Solution (FALCON PHARMACEUTICALS): 10/$59.99 or 30/$159.96

Ciprofloxacin HCl 0.3% Solution (FALCON PHARMACEUTICALS): 2/$19.99 or 7/$45.97

Disclaimer

This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.

The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.

AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions July 2006. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

1. Alcon Laboratories. Ciloxan (ciprofloxacin hydrochloride) ophthalmic solution prescribing information. Fort Worth, TX; 1999 Dec.

2. Alcon Laboratories. Product information form for American hospital formulary service: Ciloxan (ciprofloxacin HCl) 0.3% as base sterile ophthalmic solution. Fort Worth, TX: 1991 Mar.

3. Alcon Laboratories. Ciloxan product monograph. Ciloxan (ciprofloxacin HCl) 0.3% as base sterile ophthalmic solution. Fort Worth, TX: 1991 Apr.

4. Anon. Ophthalmic ciprofloxacin. Med Lett Drugs Ther. 1991; 33:52-3. [PubMed 2030657]

5. Campoli-Richards DM, Monk JP, Price A et al. Ciprofloxacin: a review of its antibacterial activity, pharmacokinetic properties and therapeutic use. Drugs. 1988; 35:373-447. [IDIS 240961] [PubMed 3292209]

6. Neu HC. Microbiologic aspects of fluoroquinolones. Am J Ophthalmol. 1991; 112:15-24S. [IDIS 284787] [PubMed 1882916]

7. Hooper DC. Mechanisms of action and resistance of older and newer fluoroquinolones. Clin Infect Dis. 2000; 31(Suppl 2):S24-8. [IDIS 454408] [PubMed 10984324]

8. Vance-Bryan K, Guay DRP, Rotschafer JC. Clinical pharmacokinetics of ciprofloxacin. Clin Pharmacokinet. 1990; 19:434-61. [PubMed 2292168]

9. Reidy JJ, Hobden JA, Hill JM et al. The efficacy of topical ciprofloxacin and norfloxacin in the treatment of experimental pseudomonas keratitis. Cornea. 1991; 10:25-8. [PubMed 1902152]

10. McDermott ML, Tran TD, Cowden JW et al. Corneal stromal penetration of topical ciprofloxacin in humans. Ophthalmology. 1993; 100:197-200. [PubMed 8437827]

11. O’Brien TP, Sawusch MR, Dick JD et al. Topical ciprofloxacin treatment of pseudomonas keratitis in rabbits. Arch Ophthalmol. 1988; 106:1444-6. [PubMed 3140772]

12. Rootman DS, Savage P, Hasany SM et al. Toxicity and pharmacokinetics of intravitreally injected ciprofloxacin in rabbit eyes. Can J Ophthalmol. 1992; 27:277-82. [PubMed 1451014]

13. Behrens-Baumann W, Martell J. Ciprofloxacin concentration in the rabbit aqueous humor and vitreous following intravenous and subconjuctival administration. Infection. 1988; 16:54-7. [PubMed 3360498]

14. Skoutelis AT, Gartaganis SP, Chrysanthopoulos CJ et al. Aqueous humor penetration of ciprofloxacin in the human eye. Arch Ophthalmol. 1988; 106:404-5. [IDIS 239150] [PubMed 3345156]

15. Bron A, Talon D, Cellier T et al. La ciprofloxacine: pénétration intra-camérulaire chez l’homme. Bull Soc Opht France. 1990; 40:805-11.

16. Sweeney G, Fern AI, Lindsay G et al. Penetration of ciprofloxacin into the aqueous humour of the uninflamed human eye after oral administration. Br Soc Antimicrob Chemother. 1990; 26:99-105.

17. Barza M. Use of quinolones for treatment of ear and eye infections. Eur J Clin Microbiol Infect Dis. 1991; 10:296-303. [PubMed 1864290]

18. El Baba FZ, Trousdale MD, Gauderman WJ et al. Intravitreal penetration of oral ciprofloxacin in humans. Ophthalmology. 1992; 99:483-6. [PubMed 1584563]

19. Gardner DK, Gabbe SG, Harter C. Simultaneous concentrations of ciprofloxacin in breast milk and in serum in mother and breast-fed infant. Clin Pharm. 1992; 11: 352-4. [IDIS 292898] [PubMed 1563233]

20. Cover DL, Mueller BA. Ciprofloxacin penetration into human breast milk: a case report. DICP. 1990; 24:703-4. [IDIS 268094] [PubMed 2375140]

21. Giamarellou H, Kanellas D, Kavouklis E et al. Comparative pharmacokinetics of ciprofloxacin, ofloxacin and pefloxacin in human aqueous humour. Eur J Clin Microbiol Infect Dis. 1993; 12:293-7. [PubMed 8513819]

22. Limberg MB. A review of bacterial keratitis and bacterial conjunctivitis. Am J Ophthalmol. 1991; 112:2-9S.

23. McDonnell PJ, Green WR. Conjunctivitis. In: Mandell GL, Douglas RG Jr, Bennett JE, eds. Principles and practices of infectious diseases. 3rd ed. New York: Churchill Livingstone; 1990:975-82.

24. Steinert RF. Current therapy for bacterial keratitis and bacterial conjunctivitis. Am J Ophthalmol. 1991; 112:10-4S.

25. Leibowitz HM. Clinical evaluation of ciprofloxacin 0.3% ophthalmic solution for treatment of bacterial keratitis. Am J Ophthalmol. 1991; 112:34-47S. [IDIS 288796] [PubMed 1882919]

26. Cokingtin CD, Hyndiuk RA. Insights from experimental data on ciprofloxacin in the treatment of bacterial keratitis and ocular infections. Am J Ophthalmol. 1991; 112:25-8S.

27. Insler MS, Fish LA, Silbernagel J et al. Successful treatment of methicillin-resistant Staphylococcus aureus keratitis with topical ciprofloxacin. Ophthalmology. 1991; 98:1690-2. [PubMed 1800931]

28. Sossi N, Feldman RM, Feldman ST et al. Mycobacterium gordonae keratitis after penetrating keratoplasty. Arch Ophthalmol. 1991; 109:1064-5. [IDIS 286440] [PubMed 1867541]

29. Hwang DG, Biswell R. Ciprofloxacin therapy of Mycobacterium chelonae keratitis. Am J Ophthalmol. 1993; 115:114-5. [IDIS 308488] [PubMed 8420364]

30. Nix DE, Devito JM. Ciprofloxacin and norfloxacin, two fluoroquinolone antimicrobials. Clin Pharm. 1987; 6:105-17. [IDIS 225594] [PubMed 3311572]

31. Wolfson JS, Hooper DC. The fluoroquinolones: structures, mechanisms of action and resistance, and spectra of activity in vitro. Antimicrob Agents Chemother. 1985; 28:581-6. [IDIS 207617] [PubMed 3000292]

32. Janknegt R. Fluorinated quinolones: a review of their mode of action, antimicrobial activity, pharmacokinetics and clinical efficacy. Pharm Weekbl [Sci]. 1986; 8:1-21. [IDIS 213999] [PubMed 3515312]

33. Verbist L. Quinolones: pharmacology. Pharm Weekbl [Sci]. 1986; 8:22-5. [IDIS 214000] [PubMed 3008075]

34. Neuman M. Clinical pharmacokinetics of the newer antibacterial 4-quinolones. Clin Pharmacokinet. 1988; 14:96-121. [IDIS 240310] [PubMed 3282749]

35. Jack DB. Recent advances in pharmaceutical chemistry: the 4-quinolone antibiotics. J Clin Hosp Pharm. 1986; 11:75-93. [IDIS 216892] [PubMed 3519688]

36. Bergan T. Quinolones. In: Peterson PK, Verhoef J, eds. The antimicrobial agents annual/1. Amsterdam: Elsevier Science Publishers BV; 1986: 164-78.

37. Miles. Cipro tablets (ciprofloxacin HCl) product monograph. West Haven, CT: 1987.

38. Crumplin GC. Aspects of chemistry in the development of the 4-quinolone antibacterial agents. Rev Infect Dis. 1988; 10(Suppl 1):S2-9. [IDIS 311592] [PubMed 3279494]

39. Miles Inc, West Haven, CT: Personal communication.

40. Kayser FH, Novak J. In vitro activity of ciprofloxacin against gram-positive bacteria: an overview. Am J Med. 1987; 82(Suppl 4A):33-9. [IDIS 230495] [PubMed 3555058]

41. Lagast H, Husson M, Klastersky J. Bactericidal activity of ciprofloxacin in serum and urine against Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Staphylococcus aureus and Streptococcus faecalis. J Antimicrob Chemother. 1985; 16:341-7. [PubMed 2932416]

42. Eliopoulos GM, Gardella A, Moellering RC. In vitro activity of ciprofloxacin, a new carboxyquinoline antimicrobial agent. Antimicrob Agents Chemother. 1984; 25:331-5. [IDIS 183089] [PubMed 6721464]

43. Smith JT. The mode of action of 4-quinolones and possible mechanisms of resistance. J Antimicrob Chemother. 1986; 18(Suppl D):21-9. [PubMed 3542946]

44. Hooper DC, Wolfson JS, Ng EY et al. Mechanisms of action of and resistance to ciprofloxacin. Am J Med. 1987; 82(Suppl 4A):12-20. [IDIS 230492] [PubMed 3034057]

45. Reeves DS, Bywater MJ, Holt HA et al. In vitro studies with ciprofloxacin, a new 4-quinolone compound. J Antimicrob Chemother. 1984; 13:333-6. [IDIS 205465] [PubMed 6233250]

46. Terp DK, Rybak MJ. Ciprofloxacin. Drug Intell Clin Pharm. 1987; 21:568-74. [IDIS 232480] [PubMed 3301247]

47. Standiford HC, Drusano GL, Forrest A et al. Bactericidal activity of ciprofloxacin compared with that of cefotaxime in normal volunteers. Antimicrob Agents Chemother. 1987; 31:1177-82. [IDIS 234803] [PubMed 3631942]

48. Thadepalli H, Bansal MB, Rao B et al. Ciprofloxacin: in vitro, experimental, and clinical evaluation. Rev Infect Dis. 1988; 10:505-15. [IDIS 309934] [PubMed 3393781]

49. Diver JM, Wise R. Morphological and biochemical changes in Escherichia coli after exposure to ciprofloxacin. J Antimicrob Chemother. 1986; 18(Suppl D):31-41. [PubMed 3542947]

50. Domagala JM, Hanna LD, Heifetz CL et al. New structure-activity relationships of the quinolone antibacterials using the target enzyme: the development and application of a DNA gyrase assay. J Med Chem. 1986; 29:394-404. [IDIS 212485] [PubMed 3005575]

51. Zweerink MM, Edison A. Inhibition of Micrococcus luteus DNA gyrase by norfloxacin and 10 other quinolone carboxylic acids. Antimicrob Agents Chemother. 1986; 29:598-601. [IDIS 215018] [PubMed 3010848]

52. Hussy P, Maass G, Tummler B et al. Effect of 4-quinolones and novobiocin on calf thymus DNA polymerase α-primase complex, topoisomerases I and II, and growth of mammalian lymphoblasts. Antimicrob Agents Chemother. 1986; 29:1073-8. [PubMed 3015015]

53. Bearden DT, Danziger LH. Mechanism of Action of and resistance to quinolones. Pharmacotherapy. 2001; 21:224S-32S [IDIS 472236] [PubMed 11642689]

54. Sanders CC. Ciprofloxacin: in vitro activity, mechanism of action, and resistance. Rev Infect Dis. 1988; 10:516-27. [IDIS 309935] [PubMed 3293157]

59. Smith SM, Eng RH, Berman E. The effect of ciprofloxacin on methicillin-resistant Staphylococcus aureus. J Antimicrob Chemother. 1986; 17:287-95. [PubMed 2939049]

60. Smith SM, Eng RH. Activity of ciprofloxacin against methicillin-resistant Staphylococcus aureus. Antimicrob Agents Chemother. 1985; 688-91. (IDIS 200502)

61. King A, Shannon K, Phillips I. The in-vitro activity of ciprofloxacin compared with that of norfloxacin and nalidixic acid. J Antimicrob Chemother. 1984; 13:325-31. [IDIS 223947] [PubMed 6233249]

62. Barry AL, Jones RN. In vitro activity of ciprofloxacin against gram-positive cocci. Am J Med. 1987; 82(Suppl 4A):27-32. [IDIS 230494] [PubMed 3578323]

63. Chau PY, Leung YK, Ng WW. Comparative in vitro antibacterial activity of ofloxacin and ciprofloxacin against some selected gram-positive and gram-negative isolates. Infection. 1986; 14(Suppl 4):S237-9. [PubMed 3469153]

64. Mandell W, Neu HC. In vitro activity of CI-934, a new quinolone, compared with that of other quinolones and other antimicrobial agents. Antimicrob Agents Chemother. 1986; 29:852-7. [PubMed 3729343]

65. Chin NX, Brittain DC, Neu HC. In vitro activity of Ro 23-6240, a new fluorinated 4-quinolone. Antimicrob Agents Chemother. 1986; 29:675-80. [IDIS 215029] [PubMed 3085584]

66. Fass RJ. In vitro activity of ciprofloxacin (Bay o 9867). Antimicrob Agents Chemother. 1983; 24:568-74. [IDIS 177504] [PubMed 6228192]

67. Chin NX, Neu HC. Ciprofloxacin, a quinolone carboxylic acid compound active against aerobic and anaerobic bacteria. Antimicrob Agents Chemother. 1984; 25:319-26. [IDIS 183087] [PubMed 6232895]

68. King A, Phillips I. The comparative in-vitro activity of eight newer quinolones and nalidixic acid. J Antimicrob Chemother. 1986; 18(Suppl D):1-20. [PubMed 3468100]

69. Barry AL, Jones RN, Thornsberry C et al. Antibacterial activities of ciprofloxacin, norfloxacin, oxolinic acid, cinoxacin, and nalidixic acid. Antimicrob Agents Chemother. 1984; 25:633-7. [IDIS 185381] [PubMed 6233935]

70. Young LS, Berlin OG, Inderlied CB. Activity of ciprofloxacin and other fluorinated quinolones against mycobacteria. Am J Med. 1987; 82(Suppl 4A):23-6. [IDIS 230493] [PubMed 3107379]

71. Gay JD, DeYoung DR, Roberts GD. In vitro activities of norfloxacin and ciprofloxacin against Mycobacterium tuberculosis, M. avium complex, M. chelonei, M. fortuitum, and M. kansasii. Antimicrob Agents Chemother. 1984; 26:94-6. [IDIS 187632] [PubMed 6236748]

72. Fenlon CH, Cynamon MH. Comparative in vitro activities of ciprofloxacin and other 4-quinolones against Mycobacterium tuberculosis and Mycobacterium intracellulare. Antimicrob Agents Chemother. 1986; 29:386-8. [IDIS 211610] [PubMed 2940969]

73. Aznar J, Caballero MC, Loxano MC et al. Activities of new quinoline derivatives against genital pathogens. Antimicrob Agents Chemother. 1985; 27:76-8. [IDIS 195272] [PubMed 3920959]

74. Ridgway GL, Mumtaz G, Gabriel FG et al. The activity of ciprofloxacin and other 4-quinolones against Chlamydia trachomatis and mycoplasmas in vitro. Eur J Clin Microbiol. 1984; 3:344-6. [IDIS 223936] [PubMed 6237903]

75. Heppleston C, Richmond S, Bailey J. Antichlamydial activity of quinolone carboxylic acids. J Antimicrob Chemother. 1985; 15:645-7. [PubMed 3159713]

76. Sanders CC, Sanders WE, Goering RV et al. Selection of multiple antibiotic resistance by quinolones, β-lactams, and aminoglycosides with special reference to cross-resistance between unrelated drug classes. Antimicrob Agents Chemother. 1984; 26:797-801. [IDIS 194031] [PubMed 6098219]

77. Barry AL, Jones RN. Cross-resistance among cinoxacin, ciprofloxacin, DJ-6783, enoxacin, nalidixic acid, norfloxacin, and oxolinic acid after in vitro selection of resistant populations. Antimicrob Agents Chemother. 1984; 25:775-7. [IDIS 223938] [PubMed 6234858]

78. Kaatz GW, Seo SM. Mechanism of ciprofloxacin resistance in Pseudomonas aeruginosa. J Infect Dis. 1988; 158:537-41. [PubMed 3137271]

79. Follath F, Bindschedler M, Wenk M et al. Use of ciprofloxacin in the treatment of Pseudomonas aeruginosa infections. Eur J Clin Microbiol. 1986; 5:236-40. [PubMed 2941289]

80. Scully BE, Parry MF, Neu HC et al. Oral ciprofloxacin therapy of infections due to Pseudomonas aeruginosa. Lancet. 1986; 1:819-22. [IDIS 214361] [PubMed 2870313]

81. Greenberg RN, Kennedy DJ, Reilly PM et al. Treatment of bone, joint, and soft-tissue infections with oral ciprofloxacin. Antimicrob Agents Chemother. 1987; 31:151-5. [IDIS 226537] [PubMed 3566245]

82. Piercy EA, Barbaro D, Luby JP et al. Ciprofloxacin for methicillin-resistant Staphylococcus aureus infections. Antimicrob Agents Chemother. 1989; 33:128-30. [IDIS 249464] [PubMed 2712546]

83. Smith SM, Eng RH, Tecson-Tumang F. Ciprofloxacin therapy for methicillin-resistant Staphylococcus aureus infections or colonizations. Antimicrob Agents Chemother. 1989; 33:181-4. [IDIS 251556] [PubMed 2719462]

87. Tartaglione TA, Raffalovich AC, Poynor WJ et al. Pharmacokinetics and tolerance of ciprofloxacin after sequential increasing oral doses. Antimicrob Agents Chemother. 1986; 29:62-6. [IDIS 212936] [PubMed 2942101]

88. Gonzalez MA, Uribe F, Moisen SD et al. Multiple-dose pharmacokinetics and safety of ciprofloxacin in normal volunteers. Antimicrob Agents Chemother. 1984; 26:741-4. [IDIS 194086] [PubMed 6517556]

89. Hoffler J, Dalhoff A, Gau W et al. Dose- and sex-independent disposition of ciprofloxacin. Eur J Clin Microbiol. 1984; 3:363-6. [PubMed 6489328]

90. Wingender W, Graege KH, Gau W et al. Pharmacokinetics of ciprofloxacin after oral and intravenous administration in healthy volunteers. Eur J Clin Microbiol. 1984; 3:355-9. [PubMed 6489326]

91. Gasser TC, Ebert SC, Graversen PH et al. Ciprofloxacin pharmacokinetics in patients with normal and impaired renal function. Antimicrob Agents Chemother. 1987; 31:709-12. [IDIS 229463] [PubMed 3300537]

92. Hoffken G, Lode H, Prinzing C et al. Pharmacokinetics of ciprofloxacin after oral and parenteral administration. Antimicrob Agents Chemother. 1985; 27:375-9. [IDIS 197548] [PubMed 3158275]

93. Bergan T, Engeset A, Olszewski W. Does serum protein binding inhibit tissue penetration of antibiotics? Rev Infect Dis. 1987; 9:713-8. (IDIS 232250)

94. Giamarellou H, Kolokythas E, Petrikkos G et al. Pharmacokinetics of three newer quinolones in pregnant and lactating women. Am J Med. 1989; 87(Suppl 5A):49-51S.

95. Zeiler HJ, Petersen U, Ploschke HJ. Antibacterial activity of the metabolites of ciprofloxacin and its significance in the bioassay. Arzneimittelforschung. 1987; 37:131-4. [PubMed 3555512]

96. Tanimura H, Tominaga S, Rai F et al. Transfer of ciprofloxacin to bile and determination of biliary metabolites in humans. Arzneimittelforschung. 1986; 26:1417-20.

97. Parry MF, Smego DA, Digiovanni MA. Hepatobiliary kinetics and excretion of ciprofloxacin. Antimicrob Agents Chemother. 1988; 32:982-5. [IDIS 244087] [PubMed 3190199]

98. Drusano GL. An overview of the pharmacology of intravenously administered ciprofloxacin. Am J Med. 1987; 82(Suppl 4A):339-45. [IDIS 230552] [PubMed 3578325]

99. Bayer. Cipro I.V. (ciprofloxacin) for intravenous infusion prescribing information. West Haven, CT; 2002 Jun.

100. Christ W, Lehnert T, Ulbrich B. Specific toxicologic aspects of the quinolones. Rev Infect Dis. 1988; 10(Suppl 1):S141-6. [IDIS 311600] [PubMed 3279489]

101. Snyder ME, Katz HR. Ciprofloxacin-resistant bacterial keratitis. Am J Ophthalmol. 1992; 114:336-8. [IDIS 301719] [PubMed 1524125]

102. Eiferman RA, Forgey DR, Snyder J. The successful treatment of bacterial corneal ulcers with ciprofloxacin. Invest Ophthalmol Vis Sci. 1991; (Suppl 32):1171.

103. Abrams DA, Sarfarazi FA, Parks DJ et al. Topical ciprofloxacin versus conventional antibiotic therapy in the treatment of ulcerative keratitis. Invest Ophthalmol Vis Sci. 1991; (Suppl 32):1171.