Crixivan

indinavir sulfate

Dosage Form: capsule
Crixivan®

(INDINAVIR SULFATE)

CAPSULES

Crixivan Description

Crixivan1 (indinavir sulfate) is an inhibitor of the human immunodeficiency virus (HIV) protease. Crixivan Capsules are formulated as a sulfate salt and are available for oral administration in strengths of 100, 200, and 400 mg of indinavir (corresponding to 125, 250, and 500 mg indinavir sulfate, respectively). Each capsule also contains the inactive ingredients anhydrous lactose and magnesium stearate. The capsule shell has the following inactive ingredients and dyes: gelatin and titanium dioxide.

The chemical name for indinavir sulfate is [1(1S,2R),5(S)] - 2,3,5 - trideoxy - N - (2,3 - dihydro - 2 - hydroxy - 1H - inden - 1 - yl) - 5 - [2 - [[(1,1 - dimethylethyl)amino]carbonyl] - 4 - (3 - pyridinylmethyl) - 1 - piperazinyl] - 2 - (phenylmethyl) - D - erythro - pentonamide sulfate (1:1) salt. Indinavir sulfate has the following structural formula:

Indinavir sulfate is a white to off-white, hygroscopic, crystalline powder with the molecular formula C36H47N5O4• H2SO4 and a molecular weight of 711.88. It is very soluble in water and in methanol.

1

Registered trademark of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.

Copyright © 1996, 1997, 1998, 1999, 2004 Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.

All rights reserved

MICROBIOLOGY

Mechanism of Action:

HIV-1 protease is an enzyme required for the proteolytic cleavage of the viral polyprotein precursors into the individual functional proteins found in infectious HIV-1. Indinavir binds to the protease active site and inhibits the activity of the enzyme. This inhibition prevents cleavage of the viral polyproteins resulting in the formation of immature non-infectious viral particles.

Antiretroviral Activity In Vitro:

The in vitro activity of indinavir was assessed in cell lines of lymphoblastic and monocytic origin and in peripheral blood lymphocytes. HIV-1 variants used to infect the different cell types include laboratory-adapted variants, primary clinical isolates and clinical isolates resistant to nucleoside analogue and nonnucleoside inhibitors of the HIV-1 reverse transcriptase. The IC95 (95% inhibitory concentration) of indinavir in these test systems was in the range of 25 to 100 nM. In drug combination studies with the nucleoside analogues zidovudine and didanosine, indinavir showed synergistic activity in cell culture. The relationship between in vitro susceptibility of HIV-1 to indinavir and inhibition of HIV-1 replication in humans has not been established.

Drug Resistance:

Isolates of HIV-1 with reduced susceptibility to the drug have been recovered from some patients treated with indinavir. Viral resistance was correlated with the accumulation of mutations that resulted in the expression of amino acid substitutions in the viral protease. Eleven amino acid residue positions, (L10l/V/R, K20l/M/R, L24l, M46l/L, l54A/V, L63P, l64V, A71T/V, V82A/F/T, l84V, and L90M), at which substitutions are associated with resistance, have been identified. Resistance was mediated by the co-expression of multiple and variable substitutions at these positions. No single substitution was either necessary or sufficient for measurable resistance (≥4-fold increase in IC95). In general, higher levels of resistance were associated with the co-expression of greater numbers of substitutions, although their individual effects varied and were not additive. At least 3 amino acid substitutions must be present for phenotypic resistance to indinavir to reach measurable levels. In addition, mutations in the p7/ p1 and p1/ p6 gag cleavage sites were observed in some indinavir resistant HIV-1 isolates.

In vitro phenotypic susceptibilities to indinavir were determined for 38 viral isolates from 13 patients who experienced virologic rebounds during indinavir monotherapy. Pre-treatment isolates from five patients exhibited indinavir IC95 values of 50-100 nM. At or following viral RNA rebound (after 12-76 weeks of therapy), IC95 values ranged from 25 to >3000 nM, and the viruses carried 2 to 10 mutations in the protease gene relative to baseline.

Cross-Resistance to Other Antiviral Agents:

Varying degrees of HIV-1 cross-resistance have been observed between indinavir and other HIV-1 protease inhibitors. In studies with ritonavir, saquinavir, and amprenavir, the extent and spectrum of cross-resistance varied with the specific mutational patterns observed. In general, the degree of cross-resistance increased with the accumulation of resistance-associated amino acid substitutions. Within a panel of 29 viral isolates from indinavir-treated patients that exhibited measurable (≥4-fold) phenotypic resistance to indinavir, all were resistant to ritonavir. Of the indinavir resistant HIV-1 isolates, 63% showed resistance to saquinavir and 81% to amprenavir.

Crixivan - Clinical Pharmacology

Pharmacokinetics

Absorption:

Indinavir was rapidly absorbed in the fasted state with a time to peak plasma concentration (Tmax) of 0.8 ± 0.3 hours (mean ± S.D.) (n=11). A greater than dose-proportional increase in indinavir plasma concentrations was observed over the 200-1000 mg dose range. At a dosing regimen of 800 mg every 8 hours, steady-state area under the plasma concentration time curve (AUC) was 30,691 ± 11,407 nM•hour (n=16), peak plasma concentration (Cmax) was 12,617 ± 4037 nM (n=16), and plasma concentration eight hours post dose (trough) was 251 ± 178 nM (n=16).

Effect of Food on Oral Absorption:

Administration of indinavir with a meal high in calories, fat, and protein (784 kcal, 48.6 g fat, 31.3 g protein) resulted in a 77% ± 8% reduction in AUC and an 84% ± 7% reduction in Cmax (n=10). Administration with lighter meals (e.g., a meal of dry toast with jelly, apple juice, and coffee with skim milk and sugar or a meal of corn flakes, skim milk and sugar) resulted in little or no change in AUC, Cmax or trough concentration.

Distribution:

Indinavir was approximately 60% bound to human plasma proteins over a concentration range of 81 nM to 16,300 nM.

Metabolism:

Following a 400-mg dose of 14C-indinavir, 83 ± 1% (n=4) and 19 ± 3% (n=6) of the total radioactivity was recovered in feces and urine, respectively; radioactivity due to parent drug in feces and urine was 19.1% and 9.4%, respectively. Seven metabolites have been identified, one glucuronide conjugate and six oxidative metabolites. In vitro studies indicate that cytochrome P-450 3A4 (CYP3A4) is the major enzyme responsible for formation of the oxidative metabolites.

Elimination:

Less than 20% of indinavir is excreted unchanged in the urine. Mean urinary excretion of unchanged drug was 10.4 ± 4.9% (n=10) and 12.0 ± 4.9% (n=10) following a single 700-mg and 1000-mg dose, respectively. Indinavir was rapidly eliminated with a half-life of 1.8 ± 0.4 hours (n=10). Significant accumulation was not observed after multiple dosing at 800 mg every 8 hours.

Special Populations

Hepatic Insufficiency:

Patients with mild to moderate hepatic insufficiency and clinical evidence of cirrhosis had evidence of decreased metabolism of indinavir resulting in approximately 60% higher mean AUC following a single 400-mg dose (n=12). The half-life of indinavir increased to 2.8 ± 0.5 hours. Indinavir pharmacokinetics have not been studied in patients with severe hepatic insufficiency (see DOSAGE AND ADMINISTRATION, Hepatic Insufficiency).

Renal Insufficiency:

The pharmacokinetics of indinavir have not been studied in patients with renal insufficiency.

Gender:

The effect of gender on the pharmacokinetics of indinavir was evaluated in 10 HIV seropositive women who received Crixivan 800 mg every 8 hours with zidovudine 200 mg every 8 hours and lamivudine 150 mg twice a day for one week. Indinavir pharmacokinetic parameters in these women were compared to those in HIV seropositive men (pooled historical control data). Differences in indinavir exposure, peak concentrations, and trough concentrations between males and females are shown in Table 1 below:

Table 1

PK Parameter	% change in PK parameter for females relative to males	90% Confidence Interval
↓Indicates a decrease in the PK parameter; ↑indicates an increase in the PK parameter.
AUC0-8h (nM•hr)	↓13%	(↓32%, ↑12%)
Cmax (nM)	↓13%	(↓32%, ↑10%)
C8h (nM)	↓22%	(↓47%, ↑15%)

The clinical significance of these gender differences in the pharmacokinetics of indinavir is not known.

Race:

Pharmacokinetics of indinavir appear to be comparable in Caucasians and Blacks based on pharmacokinetic studies including 42 Caucasians (26 HIV-positive) and 16 Blacks (4 HIV-positive).

Pediatric:

The optimal dosing regimen for use of indinavir in pediatric patients has not been established. In HIV-infected pediatric patients (age 4-15 years), a dosage regimen of indinavir capsules, 500 mg/m2 every 8 hours, produced AUC0-8hr of 38,742 ± 24,098 nM•hour (n=34), Cmax of 17,181 ± 9809 nM (n=34), and trough concentrations of 134 ± 91 nM (n=28). The pharmacokinetic profiles of indinavir in pediatric patients were not comparable to profiles previously observed in HIV-infected adults receiving the recommended dose of 800 mg every 8 hours. The AUC and Cmax values were slightly higher and the trough concentrations were considerably lower in pediatric patients. Approximately 50% of the pediatric patients had trough values below 100 nM; whereas, approximately 10% of adult patients had trough levels below 100 nM. The relationship between specific trough values and inhibition of HIV replication has not been established.

Pregnant Patients:

The optimal dosing regimen for use of indinavir in pregnant patients has not been established. A Crixivan dose of 800 mg every 8 hours (with zidovudine 200 mg every 8 hours and lamivudine 150 mg twice a day) has been studied in 16 HIV-infected pregnant patients at 14 to 28 weeks of gestation at enrollment (study PACTG 358). The mean indinavir plasma AUC0-8hr at weeks 30-32 of gestation (n=11) was 9231 nM•hr, which is 74% (95% CI: 50%, 86%) lower than that observed 6 weeks postpartum. Six of these 11 (55%) patients had mean indinavir plasma concentrations 8 hours post-dose (Cmin) below assay threshold of reliable quantification. The pharmacokinetics of indinavir in these 11 patients at 6 weeks postpartum were generally similar to those observed in non-pregnant patients in another study (see PRECAUTIONS, Pregnancy).

Drug Interactions:

(also see CONTRAINDICATIONS, WARNINGS, PRECAUTIONS, Drug Interactions)

Indinavir is an inhibitor of the cytochrome P450 isoform CYP3A4. Coadministration of Crixivan and drugs primarily metabolized by CYP3A4 may result in increased plasma concentrations of the other drug, which could increase or prolong its therapeutic and adverse effects (see CONTRAINDICATIONS and WARNINGS). Based on in vitro data in human liver microsomes, indinavir does not inhibit CYP1A2, CYP2C9, CYP2E1 and CYP2B6. However, indinavir may be a weak inhibitor of CYP2D6.

Indinavir is metabolized by CYP3A4. Drugs that induce CYP3A4 activity would be expected to increase the clearance of indinavir, resulting in lowered plasma concentrations of indinavir. Coadministration of Crixivan and other drugs that inhibit CYP3A4 may decrease the clearance of indinavir and may result in increased plasma concentrations of indinavir.

Drug interaction studies were performed with Crixivan and other drugs likely to be coadministered and some drugs commonly used as probes for pharmacokinetic interactions. The effects of coadministration of Crixivan on the AUC, Cmax and Cmin are summarized in Table 2 (effect of other drugs on indinavir) and Table 3 (effect of indinavir on other drugs). For information regarding clinical recommendations, see Table 9 in PRECAUTIONS.

Table 2: Drug Interactions: Pharmacokinetic Parameters for Indinavir in the Presence of the Coadministered Drug (See PRECAUTIONS, Table 9 for Recommended Alterations in Dose or Regimen)

Coadministered drug	Dose of Coadministered drug (mg)	Dose of Crixivan (mg)	n	Ratio (with/without coadministered drug) of Indinavir Pharmacokinetic Parameters (90% CI); No Effect = 1.00
				Cmax	AUC	Cmin
All interaction studies conducted in healthy, HIV-negative adult subjects, unless otherwise indicated.
* Relative to indinavir 800 mg three times daily alone. † Study conducted in HIV-positive subjects. ‡ Comparison to historical data on 16 subjects receiving indinavir alone. § 95% CI. ¶ Parallel group design; n for indinavir + coadministered drug, n for indinavir alone.
Cimetidine	600 twice daily, 6 days	400 single dose	12	1.07 (0.77, 1.49)	0.98 (0.81, 1.19)	0.82 (0.69, 0.99)
Clarithromycin	500 q12h, 7 days	800 three times daily, 7 days	10	1.08 (0.85, 1.38)	1.19 (1.00, 1.42)	1.57 (1.16, 2.12)
Delavirdine	400 three times daily	400 three times daily, 7 days	28	0.64* (0.48, 0.86)	No significant change*	2.18* (1.16, 4.12)
Delavirdine	400 three times daily	600 three times daily, 7 days	28	No significant change	1.53* (1.07, 2.20)	3.98* (2.04, 7.78)
Efavirenz†	600 once daily, 10 days	1000 three times daily, 10 days	20
		After morning dose		No significant change*	0.67* (0.61, 0.74)	0.61* (0.49, 0.76)
		After afternoon dose		No significant change*	0.63* (0.54, 0.74)	0.48* (0.43, 0.53)
		After evening dose		0.71* (0.57, 0.89)	0.54* (0.46, 0.63)	0.43* (0.37, 0.50)
Fluconazole†	400 once daily, 8 days	1000 three times daily, 7 days	11	0.87 (0.72, 1.05)	0.76 (0.59, 0.98)	0.90 (0.72, 1.12)
Grapefruit Juice	8 oz.	400 single dose	10	0.65 (0.53, 0.79)	0.73 (0.60, 0.87)	0.90 (0.71, 1.15)
Isoniazid	300 once daily in the morning, 8 days	800 three times daily, 7 days	11	0.95 (0.88, 1.03)	0.99 (0.87, 1.13)	0.89 (0.75, 1.06)
Itraconazole	200 twice daily, 7 days	600 three times daily, 7 days	12	0.78* (0.69, 0.88)	0.99* (0.91, 1.06)	1.49* (1.28, 1.74)
Ketoconazole	400 once daily, 7 days	600 three times daily, 7 days	12	0.69* (0.61, 0.78)	0.80* (0.74, 0.87)	1.29* (1.11, 1.51)
	400 once daily, 7 days	400 three times daily, 7 days	12	0.42* (0.37, 0.47)	0.44* (0.41, 0.48)	0.73* (0.62, 0.85)
Methadone	20-60 once daily in the morning, 8 days	800 three times daily, 8 days	10	See text below for discussion of interaction.
Quinidine	200 single dose	400 single dose	10	0.96 (0.79, 1.18)	1.07 (0.89, 1.28)	0.93 (0.73, 1.19)
Rifabutin	150 once daily in the morning, 10 days	800 three times daily, 10 days	14	0.80 (0.72, 0.89)	0.68 (0.60, 0.76)	0.60 (0.51, 0.72)
Rifabutin	300 once daily in the morning, 10 days	800 three times daily, 10 days	10	0.75 (0.61, 0.91)	0.66 (0.56, 0.77)	0.61 (0.50, 0.75)
Rifampin	600 once daily in the morning, 8 days	800 three times daily, 7 days	12	0.13 (0.08, 0.22)	0.08 (0.06, 0.11)	Not Done
Ritonavir	100 twice daily, 14 days	800 twice daily, 14 days	10, 16‡	See text below for discussion of interaction.
Ritonavir	200 twice daily, 14 days	800 twice daily,14 days	9, 16‡	See text below for discussion of interaction.
Sildenafil	25 single dose	800 three times daily	6	See text below for discussion of interaction.
St. John's wort (Hypericum perforatum, standardized to 0.3 % hypericin)	300 three times daily with meals, 14 days	800 three times daily	8	Not Available	0.46 (0.34, 0.58)§	0.19 (0.06, 0.33)§
Stavudine (d4T)†	40 twice daily, 7 days	800 three times daily, 7 days	11	0.95 (0.80, 1.11)	0.95 (0.80, 1.12)	1.13 (0.83, 1.53)
Trimethoprim/ Sulfamethoxazole	800 Trimethoprim/ 160 Sulfamethoxazole q12h, 7 days	400 four times daily, 7 days	12	1.12 (0.87, 1.46)	0.98 (0.81, 1.18)	0.83 (0.72, 0.95)
Zidovudine†	200 three times daily, 7 days	1000 three times daily, 7 days	12	1.06 (0.91, 1.25)	1.05 (0.86, 1.28)	1.02 (0.77, 1.35)
Zidovudine/ Lamivudine (3TC)†	200/150 three times daily, 7 days	800 three times daily, 7 days	6, 9¶	1.05 (0.83, 1.33)	1.04 (0.67, 1.61)	0.98 (0.56, 1.73)

Table 3: Drug Interactions: Pharmacokinetic Parameters for Coadministered Drug in the Presence of Indinavir (See PRECAUTIONS, Table 9 for Recommended Alterations in Dose or Regimen)

Coadministered drug	Dose of Coadministered drug (mg)	Dose of Crixivan (mg)	n	Ratio (with/without Crixivan) of Coadministered Drug Pharmacokinetic Parameters (90% CI); No Effect = 1.00
				Cmax	AUC	Cmin
All interaction studies conducted in healthy, HIV-negative adult subjects, unless otherwise indicated.
* Registered trademark of Ortho Pharmaceutical Corporation † Study conducted in subjects on methadone maintenance. ‡ Parallel group design; n for coadministered drug + indinavir, n for coadministered drug alone. § C6hr ¶ Study conducted in HIV-positive subjects.
Clarithromycin	500 twice daily, 7 days	800 three times daily, 7 days	12	1.19 (1.02, 1.39)	1.47 (1.30, 1.65)	1.97 (1.58, 2.46) n=11
Efavirenz	200 once daily, 14 days	800 three times daily, 14 days	20	No significant change	No significant change	--
Ethinyl Estradiol (ORTHO-NOVUM 1/35)*	35 mcg, 8 days	800 three times daily, 8 days	18	1.02 (0.96, 1.09)	1.22 (1.15, 1.30)	1.37 (1.24, 1.51)
Isoniazid	300 once daily in the morning, 8 days	800 three times daily, 8 days	11	1.34 (1.12, 1.60)	1.12 (1.03, 1.22)	1.00 (0.92, 1.08)
Methadone†	20-60 once daily in the morning, 8 days	800 three times daily, 8 days	12	0.93 (0.84, 1.03)	0.96 (0.86, 1.06)	1.06 (0.94, 1.19)
Norethindrone (ORTHO-NOVUM 1/35)*	1 mcg, 8 days	800 three times daily, 8 days	18	1.05 (0.95, 1.16)	1.26 (1.20, 1.31)	1.44 (1.32, 1.57)
Rifabutin *150 mg once daily in the morning, 11 days + indinavir compared to 300 mg once daily in the morning, 11 days alone	150 once daily in the morning, 10 days 300 once daily in the morning, 10 days	800 three times daily, 10 days 800 three times daily, 10 days	14 10	1.29 (1.05, 1.59) 2.34 (1.64, 3.35)	1.54 (1.33, 1.79) 2.73 (1.99, 3.77)	1.99 (1.71, 2.31) n=13 3.44 (2.65, 4.46) n=9
Ritonavir	100 twice daily, 14 days	800 twice daily, 14 days	10, 4‡	1.61 (1.13, 2.29)	1.72 (1.20, 2.48)	1.62 (0.93, 2.85)
	200 twice daily, 14 days	800 twice daily, 14 days	9, 5‡	1.19 (0.85, 1.66)	1.96 (1.39, 2.76)	4.71 (2.66, 8.33) n=9, 4
Saquinavir
Hard gel formulation	600 single dose	800 three times daily, 2 days	6	4.7 (2.7, 8.1)	6.0 (4.0, 9.1)	2.9 (1.7, 4.7)§
Soft gel formulation	800 single dose	800 three times daily, 2 days	6	6.5 (4.7, 9.1)	7.2 (4.3, 11.9)	5.5 (2.2, 14.1)§
Soft gel formulation	1200 single dose	800 three times daily, 2 days	6	4.0 (2.7, 5.9)	4.6 (3.2, 6.7)	5.5 (3.7, 8.3)§
Sildenafil	25 single dose	800 three times daily	6	See text below for discussion of interaction.
Stavudine¶	40 twice daily, 7 days	800 three times daily, 7 days	13	0.86 (0.73, 1.03)	1.21 (1.09, 1.33)	Not Done
Theophylline	250 single dose (on Days 1 and 7)	800 three times daily, 6 days (Days 2 to 7)	12, 4‡	0.88 (0.76, 1.03)	1.14 (1.04, 1.24)	1.13 (0.86, 1.49) n=7, 3
Trimethoprim/ Sulfamethoxazole
Trimethoprim	800 Trimethoprim/ 160 Sulfamethoxazole q12h, 7 days	400 q6h, 7 days	12	1.18 (1.05, 1.32)	1.18 (1.05, 1.33)	1.18 (1.00, 1.39)
Trimethoprim/ Sulfamethoxazole
Sulfamethoxazole	800 Trimethoprim/ 160 Sulfamethoxazole q12h, 7 days	400 q6h, 7 days	12	1.01 (0.95, 1.08)	1.05 (1.01, 1.09)	1.05 (0.97, 1.14)
Vardenafil	10 single dose	800 three times daily	18	See text below for discussion of interaction.
Zidovudine¶	200 three times daily, 7 days	1000 three times daily, 7 days	12	0.89 (0.73, 1.09)	1.17 (1.07, 1.29)	1.51 (0.71, 3.20) n=4
Zidovudine/ Lamivudine¶
Zidovudine	200/150 three times daily, 7 days	800 three times daily, 7 days	6, 7‡	1.23 (0.74, 2.03)	1.39 (1.02, 1.89)	1.08 (0.77, 1.50) n=5, 5
Zidovudine/ Lamivudine¶
Lamivudine	200/150 three times daily, 7 days	800 three times dail

Progeston

Progeston may be available in the countries listed below.

Ingredient matches for Progeston

Allylestrenol

Allylestrenol is reported as an ingredient of Progeston in the following countries:

• Indonesia

Medroxyprogesterone

Medroxyprogesterone 17α-acetate (a derivative of Medroxyprogesterone) is reported as an ingredient of Progeston in the following countries:

• Japan

Progesterone

Progesterone is reported as an ingredient of Progeston in the following countries:

• Japan

International Drug Name Search

Cutivate Cream

Pronunciation: floo-TIK-a-sone
Generic Name: Fluticasone
Brand Name: Cutivate

Cutivate Cream is used for:

Treating inflammation and itching caused by certain skin conditions. It may also be used for other conditions as determined by your doctor.

Cutivate Cream is a topical corticosteroid. It works by reducing skin inflammation (redness, swelling, itching, and irritation).

Do NOT use Cutivate Cream if:

• you are allergic to any ingredient in Cutivate Cream or to formaldehyde

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

Before using Cutivate Cream:

Some medical conditions may interact with Cutivate Cream. 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 or other substances


• if you have an acne-like rash, rosacea, inflammation around the mouth, skin thinning, a skin infection, measles, tuberculosis (TB), chickenpox, shingles, or a positive TB skin test


• if you are taking an oral corticosteroid (eg, prednisone) or similar medicines

Some MEDICINES MAY INTERACT with Cutivate Cream. However, no specific interactions with Cutivate Cream are known at this time.

Ask your health care provider if Cutivate Cream 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 Cutivate Cream:

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

• Apply a small amount of medicine to the affected area. Gently rub it in until it is evenly distributed.


• Wash your hands after you apply Cutivate Cream, unless your hands are part of the treated area.


• Do not bandage or cover the treated skin area unless directed by your doctor.


• If you miss a dose of Cutivate Cream, apply 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 apply 2 doses at once.

Ask your health care provider any questions you may have about how to use Cutivate Cream.

Important safety information:

• Cutivate Cream is for external use only. Do not get it in your eyes, nose, vagina, or mouth. If you get it in any of these areas, rinse right away with cool water.


• Do not use Cutivate Cream on the face, in the groin area, or under the armpits unless your doctor tells you otherwise.


• Do not apply Cutivate Cream in the diaper area unless your doctor tells you otherwise. If Cutivate Cream is applied to the diaper area, apply a very small amount and do not use tight-fitting undergarments or plastic pants.


• Do NOT use more than the recommended dose or use for longer than prescribed without checking with you doctor.


• If your symptoms do not get better within 2 weeks or if they get worse, check with your doctor.


• Contact your doctor if you have a cut or sore that does not heal.


• Check with your doctor before you have any vaccines while you are using Cutivate Cream.


• Do not apply Cutivate Cream over large areas of the body without first checking with your doctor.


• Do not use Cutivate Cream for other skin conditions at a later time.


• Do not use other medicines or products on your skin without first checking with your doctor.


• Overuse of topical products may worsen your condition.


• Cutivate Cream is a corticosteroid. Before you start any new medicine, check the label to see if it has a corticosteroid in it too. If it does or if you are not sure, check with your doctor or pharmacist.


• Tell your doctor or dentist that you take Cutivate Cream before you receive any medical or dental care, emergency care, or surgery.


• Serious side effects may occur if too much of Cutivate Cream is absorbed through the skin. This may be more likely to occur if you use Cutivate Cream over a large area of the body. It may also be more likely if you wrap or bandage the area after you apply Cutivate Cream. The risk is greater in children. Do not use more than the prescribed dose. Contact your doctor right away if you develop unusual weight gain (especially in the face), muscle weakness, increased thirst or urination, confusion, unusual drowsiness, severe or persistent headache, or vision changes. Discuss any questions or concerns with your doctor.


• Corticosteroids may affect growth rate in CHILDREN and teenagers in some cases. They may need regular growth checks while using a corticosteroid.


• Caution is advised when using Cutivate Cream in CHILDREN; they may be more sensitive to its effects.


• Cutivate Cream should be used with extreme caution in CHILDREN younger than 3 months 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 Cutivate Cream while you are pregnant. It is not known if Cutivate Cream is found in breast milk after topical use. If you are or will be breast-feeding while you use Cutivate Cream, check with your doctor. Discuss any possible risks to your baby.

Possible side effects of Cutivate Cream:

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:

Dryness; mild stinging, burning, or itching.

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); acne-like rash; burning, cracking, irritation, or peeling not present before you began using Cutivate Cream; excessive hair growth; inflamed hair follicles; inflammation around the mouth; thinning, softening, or discoloration 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: Cutivate 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. Symptoms may include blurred vision or other vision changes; muscle weakness; severe or persistent headache; symptoms of high blood sugar (eg, increased thirst or urination, confusion, unusual drowsiness); unusual weight gain, especially in the face.

Proper storage of Cutivate Cream:

Store Cutivate Cream between 36 and 86 degrees F (2 and 30 degrees C). Store away from heat, moisture, and light. Do not store in the bathroom. Keep Cutivate Cream out of the reach of children and away from pets.

General information:

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


• Cutivate Cream 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 Cutivate Cream. 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 Cutivate resources

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

Compare Cutivate with other medications

• Atopic Dermatitis
• Dermatologic Lesion
• Lichen Sclerosus

Crolom

cromolyn sodium

Dosage Form: ophthalmic solution
Crolom®

cromolyn sodium

ophthalmic solution USP, 4%

STERILE OPHTHALMIC SOLUTION

Rx only

DESCRIPTION:

Crolom® (cromolyn sodium ophthalmic solution USP, 4%) is a clear, colorless, sterile solution for topical ophthalmic use.

Cromolyn sodium is represented by the following structural formula:

C23H14Na2O11                                                                                                           Mol. Wt. 512.34

Chemical Name: Disodium 5,5'- [(2-hydroxytrimethylene)dioxy]bis[4-oxo-4H-1-benzopyran-2-carboxylate]

Pharmacologic Category: Mast cell stabilizer.

EACH mL CONTAINS: ACTIVE: Cromolyn Sodium 40 mg (4%); INACTIVES: Edetate Disodium 0.1% and Purified Water. Hydrochloric Acid and/or Sodium Hydroxide may be added to adjust pH (4.0 - 7.0). PRESERVATIVE ADDED: Benzalkonium Chloride 0.01%.

CLINICAL PHARMACOLOGY:

In vitro and in vivo animal studies have shown that cromolyn sodium inhibits the degranulation of sensitized mast cells which occurs after exposure to specific antigens. Cromolyn sodium acts by inhibiting the release of histamine and SRS-A (slow-reacting substance of anaphylaxis) from the mast cell.

Another activity demonstrated in vitro is the capacity of cromolyn sodium to inhibit the degranulation of nonsensitized rat mast cells by phospholipase A and the subsequent release of chemical mediators. Another study showed that cromolyn sodium did not inhibit the enzymatic activity of released phospholipase A on its specific substrate.

Cromolyn sodium has no intrinsic vasoconstrictor, antihistamine, or anti-inflammatory activity.

Cromolyn sodium is poorly absorbed. When multiple doses of cromolyn sodium ophthalmic solution are instilled into normal rabbit eyes, less than 0.07% of the administered dose of cromolyn sodium is absorbed into the systemic circulation (presumably by way of the eye, nasal passages, buccal cavity and gastrointestinal tract). Trace amounts (less than 0.01%) of the cromolyn sodium dose penetrate into the aqueous humor and clearance from this chamber is virtually complete within 24 hours after treatment is stopped.

In normal volunteers, analysis of drug excretion indicates that approximately 0.03% of cromolyn sodium is absorbed following administration to the eye.

INDICATIONS AND USAGE:

Cromolyn sodium ophthalmic solution is indicated in the treatment of vernal keratoconjunctivitis, vernal conjunctivitis, and vernal keratitis.

CONTRAINDICATIONS:

Cromolyn sodium ophthalmic solution is contraindicated in those patients who have shown hypersensitivity to cromolyn sodium or to any of the other ingredients.

PRECAUTIONS:

General:

Patients may experience a transient stinging or burning sensation following application of cromolyn sodium ophthalmic solution.

The recommended frequency of administration should not be exceeded (see DOSAGE AND ADMINISTRATION).

Information for Patients:

Patients should be advised to follow the patient instructions listed on the Information for Patients sheet.

Users of contact lenses should refrain from wearing lenses while exhibiting the signs and symptoms of vernal keratoconjunctivitis, vernal conjunctivitis, or vernal keratitis. Do not wear contact lenses during treatment with cromolyn sodium ophthalmic solution.

Carcinogenesis, Mutagenesis, Impairment of Fertility:

Long-term studies of cromolyn sodium in mice (12 months intraperitoneal administration at doses up to 150 mg/kg three days per week), hamsters (intraperitoneal administration at doses up to 52.6 mg/kg three days per week for 15 weeks followed by 17.5 mg/kg three days per week for 37 weeks), and rats (18 months subcutaneous administration at doses up to 75 mg/kg six days per week) showed no neoplastic effects. The average daily maximum dose levels administered in these studies were 192.9 mg/m2 for mice, 47.2 mg/m2 for hamsters and 385.8 mg/m2 for rats. These doses correspond to approximately 6.8, 1.7, and 14 times the maximum daily human dose of 28 mg/m2.

Cromolyn sodium showed no mutagenic potential in the Ames Salmonella/microsome plate assays, mitotic gene conversion in Saccharomyces cerevisiae and in an in vitro cytogenetic study in human peripheral lymphocytes.

No evidence of impaired fertility was shown in laboratory reproduction studies conducted subcutaneously in rats at the highest doses tested, 175 mg/kg/day (1050 mg/m2) in males and 100 mg/kg/day (600 mg/m2) in females. These doses are approximately 37 and 21 times the maximum daily human dose, respectively, based on mg/m2.

Pregnancy:

Teratogenic effects:

Pregnancy Category B. Reproduction studies with cromolyn sodium administered subcutaneously to pregnant mice and rats at maximum daily doses of 540 mg/kg (1620 mg/m2) and 164 mg/kg (984 mg/m2), respectively, and intravenously to rabbits at a maximum daily dose of 485 mg/kg (5820 mg/m2) produced no evidence of fetal malformation. These doses represent approximately 57, 35, and 205 times the maximum daily human dose, respectively, on a mg/m2 basis. Adverse fetal effects (increased resorption and decreased fetal weight) were noted only at the very high parenteral doses that produced maternal toxicity. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Nursing Mothers:

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when cromolyn sodium ophthalmic solution is administered to a nursing woman.

Pediatric Use:

Safety and effectiveness in pediatric patients below the age of 4 years have not been established.

Geriatric Use:

No overall differences in safety or effectiveness have been observed between elderly and younger patients.

ADVERSE REACTIONS:

The most frequently reported adverse reaction attributed to the use of cromolyn sodium ophthalmic solution, on the basis of reoccurrence following readministration, is transient ocular stinging or burning upon instillation.

The following adverse reactions have been reported as infrequent events. It is unclear whether they are attributed to the drug:

Conjunctival injection; watery eyes; itchy eyes; dryness around the eye; puffy eyes; eye irritation; and styes.

Immediate hypersensitivity reactions have been reported rarely and include dyspnea, edema, and rash.

DOSAGE AND ADMINISTRATION:

The dose is 1 – 2 drops in each eye 4 – 6 times a day at regular intervals.

One drop contains approximately 1.6 mg cromolyn sodium.

Patients should be advised that the effect of cromolyn sodium ophthalmic solution therapy is dependent upon its administration at regular intervals, as directed.

Symptomatic response to therapy (decreased itching, tearing, redness, and discharge) is usually evident within a few days, but longer treatment for up to six weeks is sometimes required. Once symptomatic improvement has been established, therapy should be continued for as long as needed to sustain improvement.

If required, corticosteroids may be used concomitantly with cromolyn sodium ophthalmic solution.

FOR OPHTHALMIC USE ONLY

HOW SUPPLIED:

Crolom® (cromolyn sodium ophthalmic solution USP, 4%) is supplied in a plastic bottle individually cartoned with a controlled drop tip in the following sizes:

10 mL bottle (NDC 24208-300-10) - AB30709

DO NOT USE IF IMPRINTED NECKBAND IS NOT INTACT.

Storage:

Store between 15°-30°C (59°-86°F). Protect from light – store in original carton. Keep tightly closed. Replace cap immediately after use.

KEEP OUT OF REACH OF CHILDREN.

Rx only

Bausch & Lomb Incorporated

Tampa, Florida 33637

©Bausch & Lomb Incorporated

XO50206 (Folded)

XM10005 (Flat)

R.1/04-83

Patient Instructions

PHARMACIST — DETACH HERE AND GIVE INSTRUCTIONS TO PATIENTS

Information for the Patient

Crolom®

(cromolyn sodium ophthalmic solution USP, 4%) Sterile

It is important to use Crolom® regularly, as directed by your physician.

1. Thoroughly wash your hands.

2. Remove safety seal (Figure 1).

3. Remove cap (Figure 2).

4. Sit or stand comfortably, with your head tilted back (Figure 3).

5. Open eyes, look up, and draw the lower lid of your eye down gently with your index finger (Figure 4).

6. Hold the Crolom® bottle upside down. Place dropper tip as close as possible to the lower eyelid and gently squeeze out the prescribed number of drops (Figure 5).

7. Do not touch the eye or eyelid with the dropper tip.

8. Blink a few times to make sure the eye is covered with the solution.

9. Close your eye and remove any excess solution with a clean tissue.

10. Repeat process in the other eye.

 

SPECIAL TIPS

1. Avoid placing Crolom® solution directly on the cornea (the area just over the pupil), because it is especially sensitive. You will find the administration of eye drops more comfortable if you place the drops just inside the lower eyelid as shown in Figure 5 on the previous page.

2. To avoid contamination of the solution, do not touch dropper tip to the eye, fingers or any other surface. Replace cap after use. It is recommended that any remaining contents be discarded after the treatment period prescribed by your physician.

3. Store between 15°-30°C (59°-86°F). Protect from light – store in original carton. Keep tightly closed. Replace cap immediately after use.

4. Keep out of the reach of children.

5. Do not use with any other ocular medication unless directed by your physician. Do not wear contact lenses during treatment with Crolom®.

Bausch & Lomb Incorporated

Tampa, Florida 33637

©Bausch & Lomb Incorporated

XO50206 (Folded)

XM10005 (Flat)

R.1/04-83

Principal Display Panel

NDC 24208-300-10

Bausch & Lomb

Crolom

Cromolyn Sodium Ophthalmic Solution USP, 4%

[icon- eye]

STERILE

Rx only

10 mL

Crolom  cromolyn sodium  solution/ drops

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 24208-300 Route of Administration OPHTHALMIC DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength CROMOLYN SODIUM (CROMOLYN) CROMOLYN SODIUM 40 mg  in 1 mL

Inactive Ingredients Ingredient Name Strength BENZALKONIUM CHLORIDE   EDETATE DISODIUM   HYDROCHLORIC ACID   WATER   SODIUM HYDROXIDE

Product Characteristics Color      Score      Shape Size Flavor Imprint Code Contains

Packaging # NDC Package Description Multilevel Packaging 1 24208-300-10 1 BOTTLE In 1 CARTON contains a BOTTLE, DROPPER 1 10 mL In 1 BOTTLE, DROPPER This package is contained within the CARTON (24208-300-10)

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
ANDA	ANDA074443	01/30/1995

Labeler - Bausch & Lomb Incorporated (196603781)

Establishment
Name	Address	ID/FEI	Operations
Bausch & Lomb Incorporated		807927397	MANUFACTURE

Revised: 03/2011Bausch & Lomb Incorporated

More Crolom resources

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

• Crolom Advanced Consumer (Micromedex) - Includes Dosage Information


• Crolom ophthalmic Concise Consumer Information (Cerner Multum)


• cromolyn ophthalmic Concise Consumer Information (Cerner Multum)

Compare Crolom with other medications

• Conjunctivitis, Allergic
• Keratitis
• Keratoconjunctivitis

Hexymer

Hexymer may be available in the countries listed below.

Ingredient matches for Hexymer

Trihexyphenidyl

Trihexyphenidyl hydrochloride (a derivative of Trihexyphenidyl) is reported as an ingredient of Hexymer in the following countries:

• Indonesia

International Drug Name Search

Crolom ophthalmic

Generic Name: cromolyn sodium (ophthalmic) (KROE moe lin off THAL mik)

Brand Names: Crolom, Opticrom

What is Crolom (cromolyn sodium (ophthalmic))?

Cromolyn sodium is an anti-inflammatory medication. It works by preventing the release of substances in the body that cause inflammation.

Cromolyn sodium ophthalmic (for the eyes) is used to treat allergy symptoms that affect the eyes, such as itching, burning, watering, swelling, redness, or sensitivity to light.

Cromolyn sodium ophthalmic may also be used for other purposes not listed in this medication guide.

What is the most important information I should know about Crolom (cromolyn sodium (ophthalmic))?

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

Do not allow the tip of the eye dropper to touch any surface, including the eyes or hands. If the dropper becomes contaminated it could cause an infection in your eye, which can lead to vision loss or serious damage to the eye.

It may take up to 6 weeks of using cromolyn sodium before your symptoms improve. For best results, keep using the medication as directed. Talk with your doctor if your symptoms do not improve after 6 weeks of treatment.

Do not wear contact lenses while using cromolyn sodium ophthalmic, or when you have allergy symptoms affecting your eyes.

During treatment with cromolyn sodium ophthalmic, avoid using any other eye medications that your doctor has not prescribed.

What should I tell my healthcare provider before using Crolom (cromolyn sodium (ophthalmic))?

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

If you have certain conditions, you may need a dose adjustment or special tests to safely use this medication. Before you use cromolyn sodium ophthalmic, tell your doctor about all of your medical conditions.

FDA pregnancy category B. Cromolyn sodium is not expected to be harmful to an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant during treatment. It is not known whether cromolyn sodium 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. Do not give this medication to a child younger than 4 years old.

How should I use Crolom (cromolyn sodium (ophthalmic))?

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

For best results, use this medication at regular intervals.

Wash your hands before using the eye drops.

To apply the eye drops:

• 
  

  Tilt your head back slightly and pull down your lower eyelid to create a small pocket. Hold the dropper above the eye with the dropper tip down. Look up and away from the dropper as you squeeze out a drop, then close your eye.

  
  


• 
  

  Use only the number of drops your doctor has prescribed.

  
  


• 
  

  Gently press your finger to the inside corner of the eye (near your nose) for about 1 minute to keep the liquid from draining into your tear duct. If you use more than one drop in the same eye, wait about 5 minutes before putting in the next drop.

  
  


• 
  

  Do not allow the dropper tip to touch any surface, including the eyes or hands. If the dropper becomes contaminated it could cause an infection in your eye, which can lead to vision loss or serious damage to the eye.

  
  

It may take up to 6 weeks of using cromolyn sodium before your symptoms improve. For best results, keep using the medication as directed. Talk with your doctor if your symptoms do not improve after 6 weeks of treatment.

Store cromolyn sodium ophthalmic at room temperature away from moisture, heat, and light. Keep the bottle tightly closed when not in use.

What happens if I miss a dose?

Use the missed dose as soon as you remember. If it is almost time for your next dose, wait until then to use the medicine and skip the missed dose. Do not use 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 this medication is not expected to produce serious side effects.

What should I avoid while using Crolom (cromolyn sodium (ophthalmic))?

Do not wear contact lenses while using this medication, or when you have allergy symptoms affecting your eyes.

During treatment with cromolyn sodium ophthalmic, avoid using any other eye medications that your doctor has not prescribed.

Crolom (cromolyn sodium (ophthalmic)) 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.

Stop using this medication and call your doctor if you have severe burning, stinging, or irritation in your eyes after using the eye drops.

Less serious side effects may include:

• 
  

  mild burning or stinging after you use the eye drops;

  
  


• 
  

  dry or irritated eyes;

  
  


• 
  

  puffy eyes; or

  
  


• 
  

  watery eyes.

  
  

This is not a complete list of side effects and others may occur. Tell your doctor about any unusual or bothersome side effect. You may report side effects to FDA at 1-800-FDA-1088.

What other drugs will affect Crolom (cromolyn sodium (ophthalmic))?

It is not likely that other drugs you take orally or inject will have an effect on cromolyn sodium used in the eyes. But many drugs can interact with each other. 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 Crolom resources

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

Compare Crolom with other medications

• Conjunctivitis, Allergic
• Keratitis
• Keratoconjunctivitis

Where can I get more information?

• Your pharmacist can provide more information about cromolyn sodium ophthalmic.

See also: Crolom side effects (in more detail)

Cyclogyl

cyclopentolate hydrochloride

Dosage Form: ophthalmic solution
Cyclogyl®

(cyclopentolate hydrochloride ophthalmic solution, USP)

DESCRIPTION

Cyclogyl® (cyclopentolate hydrochloride ophthalmic solution, USP) is an anticholinergic prepared as a sterile, borate buffered, solution for topical ocular use. It is supplied in three strengths. The active ingredient is represented by the structural formula:

Molecular Weight=327.85

Molecular Formula: C17H25NO3•HCl

Established name: Cyclopentolate Hydrochloride

Chemical name: 2-(Dimethylamino)ethyl 1-hydroxy-α-phenylcyclopentaneacetate hydrochloride

Each mL contains: Active: cyclopentolate hydrochloride 0.5%, 1% or 2%. Preservative: benzalkonium chloride 0.01%. Inactives: boric acid, edetate disodium, potassium chloride (except 2% strength), sodium carbonate and/or hydrochloric acid (to adjust pH), purified water. The pH range is between 3.0 and 5.5.

CLINICAL PHARMACOLOGY

This anticholinergic preparation blocks the responses of the sphincter muscle of the iris and the accommodative muscle of the ciliary body to cholinergic stimulation, producing papillary dilation (mydriasis) and paralysis of accommodation (cycloplegia). It acts rapidly, but has a shorter duration than atropine. Maximal cycloplegia occurs within 25 to 75 minutes after instillation. Complete recovery of accommodation usually takes 6 to 24 hours. Complete recovery from mydriasis in some individuals may require several days. Heavily pigmented irides may require more doses than lightly pigmented irides.

INDICATIONS AND USAGE

Cyclopentolate hydrochloride is used to produce mydriasis and cycloplegia.

CONTRAINDICATIONS

Should not be used when untreated narrow-angle glaucoma, or untreated anatomically narrow angles are present, or if the patient is hypersensitive to any component of this preparation.

WARNINGS

FOR TOPICAL OPHTHALMIC USE ONLY. NOT FOR INJECTION. This preparation may cause CNS disturbances. This is especially true in younger age groups, but may occur at any age, especially with the stronger solutions. Infants are especially prone to CNS and cardiopulmonary side effects from cyclopentolate. To minimize absorption, use only 1 drop of 0.5% Cyclogyl solution per eye, followed by pressure applied over the nasolacrimal sac for two to three minutes. Observe infants closely for at least 30 minutes following instillation.

Mydriatics may produce a transient elevation of intraocular pressure.

PRECAUTIONS

General

The lacrimal sac should be compressed by digital pressure for two to three minutes after instillation to reduce excessive systemic absorption. Caution should be observed when considering use of this medication in the presence of Down's syndrome and in those predisposed to angle-closure glaucoma.

Information for Patients

Do not touch dropper tip to any surface, as this may contaminate the solution. A transient burning sensation may occur upon instillation. Patients should be advised not to drive or engage in other hazardous activities while pupils are dilated. Patients may experience sensitivity to light and should protect eyes in bright illumination during dilation. Parents should be warned not to get this preparation in their child's mouth and to wash their own hands and the child's hands following administration. Feeding intolerance may follow ophthalmic use of this product in infants. It is recommended that feeding be withheld for four (4) hours after examination.

Drug Interactions

Cyclopentolate may interfere with the ocular anti-hypertensive action of carbachol, pilocarpine, or ophthalmic cholinesterase inhibitors.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Studies in animals or humans have not been conducted to evaluate the carcinogenic potential of Cyclogyl® (cyclopentolate hydrochloride ophthalmic solution, USP).

Pregnancy

Pregnancy Category C. Animal reproduction studies have not been conducted with cyclopentolate. It is also not known whether cyclopentolate can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Cyclopentolate should be administered to a pregnant woman only if clearly needed.

Nursing Mothers

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

Pediatric Use

Use of cyclopentolate has been associated with psychotic reactions and behavioral disturbances in pediatric patients. Increased susceptibility to cyclopentolate has been reported in infants, young children, and in children with spastic paralysis or brain damage. These disturbances include ataxia, incoherent speech, restlessness, hallucinations, hyperactivity, seizures, disorientation as to time and place, and failure to recognize people. Feeding intolerance may follow ophthalmic use of this product in infants. It is recommended that feeding be withheld for four (4) hours after examination. Observe infants closely for at least 30 minutes (See WARNINGS).

Geriatric Use

No overall differences in safety or effectiveness have been observed between elderly and younger patients.

ADVERSE REACTIONS

Ocular: Increased intraocular pressure, burning, photophobia, blurred vision, irritation, hyperemia, conjunctivitis, blepharoconjunctivitis, punctate keratitis, synechiae have been reported.

Non-ocular: Use of cyclopentolate has been associated with psychotic reactions and behavioral disturbances, usually in children, especially with 2% concentration. These disturbances include ataxia, incoherent speech, restlessness, hallucinations, hyperactivity, seizures, disorientation as to time and place, and failure to recognize people. This drug produces reactions similar to those of other anticholinergic drugs, but the central nervous system manifestations as noted above are more common. Other toxic manifestations of anticholinergic drugs are skin rash, abdominal distention in infants, unusual drowsiness, tachycardia, hyperpyrexia, vasodilation, urinary retention, diminished gastrointestinal motility and decreased secretion in salivary and sweat glands, pharynx, bronchi and nasal passages. Severe manifestations of toxicity include coma, medullary paralysis and death.

OVERDOSAGE

Excessive dosage may produce behavioral disturbances, tachycardia, hyperpyrexia, hypertension, elevated intraocular pressure, vasodilation, urinary retention, diminished gastrointestinal motility and decreased secretion in salivary and sweat glands, pharynx, bronchi and nasal passages. Patients exhibiting signs of overdosage should receive supportive care and monitoring.

DOSAGE AND ADMINISTRATION

Adults: Instill one or two drops of 0.5%, 1% or 2% solution in the eye which may be repeated in five to ten minutes if necessary. Complete recovery usually occurs in 24 hours. Complete recovery from mydriasis in some individuals may require several days. Children: Instill one or two drops of 0.5%, 1% or 2% solution in the eye which may be repeated five to ten minutes later by a second application of 0.5% or 1% solution if necessary. Small Infants: A single instillation of one drop of 0.5% in the eye. To minimize absorption, apply pressure over the nasolacrimal sac for two to three minutes. Observe infant closely for at least 30 minutes following instillation. Individuals with heavily pigmented irides may require higher strengths.

HOW SUPPLIED

In multiple-dose plastic DROP-TAINER® dispensers:

      0.5% Cyclogyl                  1% Cyclogyl                    2% Cyclogyl

15 mL NDC 0065-0395-15    2 mL NDC 0065-0396-02      2 mL NDC 0065-0397-02

                                                5 mL NDC 0065-0396-05      5 mL NDC 0065-0397-05

                                              15 mL NDC 0065-0396-15    15 mL NDC 0065-0397-15

Storage: Store at 8° - 27°C (46° - 80°F).

Rx Only

Revised: February 2004

©2004 Alcon, Inc

249038-0204

ALCON LABORATORIES, INC.

Fort Worth, Texas 76134 USA

Printed in USA

PRINCIPAL DISPLAY PANEL

NDC 0065-0397-05

Alcon®

Cyclogyl®

2%

(cyclopentolate

hydrochloride

ophthalmic

solution, USP)

5 mL Sterile

Cyclogyl  cyclopentolate hydrochloride  solution

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 0065-0395 Route of Administration OPHTHALMIC DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength CYCLOPENTOLATE HYDROCHLORIDE (CYCLOPENTOLATE) CYCLOPENTOLATE HYDROCHLORIDE 5 mg  in 1 mL

Inactive Ingredients Ingredient Name Strength BENZALKONIUM CHLORIDE   BORIC ACID   EDETATE DISODIUM   SODIUM CARBONATE   HYDROCHLORIC ACID   WATER   POTASSIUM CHLORIDE

Product Characteristics Color      Score      Shape Size Flavor Imprint Code Contains

Packaging # NDC Package Description Multilevel Packaging 1 0065-0395-15 15 mL In 1 BOTTLE, PLASTIC None

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
ANDA	ANDA084108	10/15/1975

Cyclogyl  cyclopentolate hydrochloride  solution

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 0065-0396 Route of Administration OPHTHALMIC DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength CYCLOPENTOLATE HYDROCHLORIDE (CYCLOPENTOLATE) CYCLOPENTOLATE HYDROCHLORIDE 10 mg  in 1 mL

Inactive Ingredients Ingredient Name Strength BENZALKONIUM CHLORIDE   BORIC ACID   EDETATE DISODIUM   SODIUM CARBONATE   HYDROCHLORIC ACID   WATER   POTASSIUM CHLORIDE

Product Characteristics Color      Score      Shape Size Flavor Imprint Code Contains

Packaging # NDC Package Description Multilevel Packaging 1 0065-0396-02 2 mL In 1 BOTTLE, PLASTIC None 2 0065-0396-05 5 mL In 1 BOTTLE, PLASTIC None 3 0065-0396-15 15 mL In 1 BOTTLE, PLASTIC None

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
ANDA	ANDA084108	10/15/1975

Cyclogyl  cyclopentolate hydrochloride  solution

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 0065-0397 Route of Administration OPHTHALMIC DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength CYCLOPENTOLATE HYDROCHLORIDE (CYCLOPENTOLATE) CYCLOPENTOLATE HYDROCHLORIDE 20 mg  in 1 mL

Inactive Ingredients Ingredient Name Strength BENZALKONIUM CHLORIDE   BORIC ACID   EDETATE DISODIUM   SODIUM CARBONATE   HYDROCHLORIC ACID   WATER

Product Characteristics Color      Score      Shape Size Flavor Imprint Code Contains

Packaging # NDC Package Description Multilevel Packaging 1 0065-0397-02 2 mL In 1 BOTTLE, PLASTIC None 2 0065-0397-05 5 mL In 1 BOTTLE, PLASTIC None 3 0065-0397-15 15 mL In 1 BOTTLE, PLASTIC None

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
ANDA	ANDA084108	10/15/1975

Labeler - Alcon Laboratories, Inc. (008018525)

Registrant - Alcon Laboratories, Inc. (008018525)

Establishment
Name	Address	ID/FEI	Operations
Alcon Laboratories, Inc.		008018525	MANUFACTURE

Revised: 08/2011Alcon Laboratories, Inc.

More Cyclogyl resources

• Cyclogyl Side Effects (in more detail)
• Cyclogyl Dosage
• Cyclogyl Use in Pregnancy & Breastfeeding
• Cyclogyl Drug Interactions
• Cyclogyl Support Group
• 1 Review for Cyclogyl - Add your own review/rating

• Cyclogyl Concise Consumer Information (Cerner Multum)


• Cyclogyl Ophthalmic Advanced Consumer (Micromedex) - Includes Dosage Information


• Cyclogyl MedFacts Consumer Leaflet (Wolters Kluwer)


• Cylate Advanced Consumer (Micromedex) - Includes Dosage Information

Compare Cyclogyl with other medications

• Pupillary Dilation
• Refraction, Assessment
• Uveitis