Ketorolac Injection

Generic Name: ketorolac tromethamine

Dosage Form: injection, solution
KETOROLAC

TROMETHAMINE

INJECTION, USP

I.V./I.M.

Rx only

WARNING

Ketorolac tromethamine, a nonsteroidal anti-inflammatory drug (NSAID), is indicated for the short-term (up to 5 days) management of moderately severe, acute pain, that requires analgesia at the opioid level. It is NOT indicated for minor or chronic painful conditions. Ketorolac tromethamine is a potent NSAID analgesic, and its administration carries many risks. The resulting NSAID-related adverse events can be serious in certain patients for whom ketorolac tromethamine is indicated, especially when the drug is used inappropriately. Increasing the dose of ketorolac tromethamine beyond the label recommendations will not provide better efficacy but will result in increasing the risk of developing serious adverse events.

Gastrointestinal Effects

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  Ketorolac tromethamine can cause peptic ulcers, gastrointestinal bleeding, and/or perforation. Therefore, ketorolac tromethamine is CONTRAINDICATED in patients with active peptic ulcer disease, in patients with recent gastrointestinal bleeding or perforation, and in patients with a history of peptic ulcer disease or gastrointestinal bleeding.

  
  

Renal Effects

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  Ketorolac tromethamine is CONTRAINDICATED in patients with advanced renal impairment and in patients at risk for renal failure due to volume depletion (see WARNINGS).

  
  

Risk of Bleeding

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  Ketorolac tromethamine inhibits platelet function and is, therefore, CONTRAINDICATED in patients with suspected or confirmed cerebrovascular bleeding, patients with hemorrhagic diathesis, incomplete hemostasis, and those at high risk of bleeding (see WARNINGS and PRECAUTIONS).

  
  


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  Ketorolac tromethamine is CONTRAINDICATED as prophylactic analgesic before any major surgery, and is CONTRAINDICATED intra-operatively when hemostasis is critical because of the increased risk of bleeding.

  
  

Hypersensitivity

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  Hypersensitivity reactions, ranging from bronchospasm to anaphylactic shock, have occurred and appropriate counteractive measures must be available when administering the first dose of ketorolac tromethamine injection (see CONTRAINDICATIONS and WARNINGS). Ketorolac tromethamine is CONTRAINDICATED in patients with previously demonstrated hypersensitivity to ketorolac tromethamine or allergic manifestations to aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs).

  
  

Intrathecal or Epidural Administration

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  Ketorolac tromethamine is CONTRAINDICATED for intrathecal or epidural administration due to its alcohol content.

  
  

Labor, Delivery and NURSING

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  The use of ketorolac tromethamine in labor and delivery is CONTRAINDICATED because it may adversely affect fetal circulation and the uterus.

  
  


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  The use of ketorolac tromethamine is CONTRAINDICATED in nursing mothers because of the potential adverse effects of prostaglandin-inhibiting drugs on neonates.

  
  

Concomitant Use with NSAIDs

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  Ketorolac tromethamine is CONTRAINDICATED in patients currently receiving ASA or NSAIDs because of the cumulative risk of inducing serious NSAID-related side effects.

  
  

DOSAGE AND ADMINISTRATION

Ketorolac Tromethamine Tablets

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  Ketorolac tromethamine tablets are indicated only as continuation therapy to ketorolac tromethamine injection, and the combined duration of use of ketorolac tromethamine injection and ketorolac tromethamine tablets is not to exceed 5 (five) days, because of the increased risk of serious adverse events.

  
  


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  The recommended total daily dose of ketorolac tromethamine tablets (maximum 40 mg) is significantly lower than for ketorolac tromethamine injection (maximum 120 mg) (see DOSAGE AND ADMINISTRATION and Transition from ketorolac tromethamine injection to ketorolac tromethamine tablets).

  
  

Special Populations

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  Dosage should be adjusted for patients 65 years or older, for patients under 50 kg (110 lbs) of body weight (see DOSAGE AND ADMINISTRATION), and for patients with moderately elevated serum creatinine (see WARNINGS). Doses of ketorolac tromethamine injection are not to exceed 60 mg (total dose per day) in these patients.

  
  

Ketorolac Injection Description

Ketorolac tromethamine is a member of the pyrrolo-pyrrole group of nonsteroidal anti-inflammatory drugs (NSAIDs). The chemical name for ketorolac tromethamine is (±)-5-benzoyl-2,3-dihydro-1H-pyrrolizine-1-carboxylic acid, compound with 2-amino-2-(hydroxymethyl)-1,3-propanediol, and the structural formula is presented in Figure 1.

FIGURE 1

Ketorolac tromethamine is a racemic mixture of [-]S and [+]R ketorolac tromethamine. Ketorolac tromethamine may exist in three crystal forms. All forms are equally soluble in water. Ketorolac tromethamine has a pKa of 3.5 and an n-octanol/water partition coefficient of 0.26. The molecular weight of ketorolac tromethamine is 376.41.

Ketorolac tromethamine is available for intravenous (IV) or intramuscular (IM) administration as 15 mg per mL (1.5%) and 30 mg per mL (3%) in sterile solution; 60 mg per 2 mL (3%) of ketorolac tromethamine in sterile solution is available for IM administration only. The solutions contain 10% (w/v) alcohol, and 6.68 mg, 4.35 mg, and 8.7 mg, respectively, of sodium chloride in sterile water. May contain sodium hydroxide and/or hydrochloric acid for pH adjustment, pH 7.4 (6.9 to 7.9). The sterile solutions are clear and slightly yellow in color.

Ketorolac Injection - Clinical Pharmacology

PHARMACODYNAMICS

Ketorolac tromethamine is a nonsteroidal anti-inflammatory drug (NSAID). Ketorolac tromethamine inhibits synthesis of prostaglandins and may be considered a peripherally-acting analgesic. The biological activity of ketorolac tromethamine is associated with the S-form. Ketorolac tromethamine possesses no sedative or anxiolytic properties.

Pain relief was statistically different after ketorolac tromethamine dosing from that of placebo at 1/2 hour (the first time point at which it was measured) following the largest recommended doses of ketorolac tromethamine, and by 1 hour following the smallest recommended doses. The peak analgesic effect occurred within 2 to 3 hours and was not statistically significantly different over the recommended dosage range of ketorolac tromethamine. The greatest difference between large and small doses of ketorolac tromethamine by either route was in the duration of analgesia.

PHARMACOKINETICS

Ketorolac tromethamine is a racemic mixture of [-]S- and [+]R-enantiomeric forms, with the S-form having analgesic activity.

Comparison of IV, IM and Oral Pharmacokinetics

The pharmacokinetics of ketorolac tromethamine, following IV, IM, and oral doses of ketorolac tromethamine, are compared in Table 1. The extent of bioavailability following administration of the oral and IM forms of ketorolac tromethamine was equal to that following an IV bolus.

Linear Kinetics

Following administration of single oral, IM or IV dose of ketorolac tromethamine, in the recommended dosage ranges, the clearance of the racemate does not change. This implies that the pharmacokinetics of ketorolac tromethamine in humans, following single or multiple IM, IV or recommended oral doses of ketorolac tromethamine, are linear. At the higher recommended doses, there is a proportional increase in the concentrations of free and bound racemate.

Binding and Distribution

The ketorolac tromethamine racemate has been shown to be highly protein-bound (99%). Nevertheless, even plasma concentrations as high as 10 mcg/mL will only occupy approximately 5% of the albumin binding sites. Thus, the unbound fraction for each enantiomer will be constant over the therapeutic range. A decrease in serum albumin, however, will result in increased free drug concentrations.

The mean apparent volume (Vβ) of ketorolac tromethamine following complete distribution was approximately 13 liters. This parameter was determined from single-dose data.

Metabolism

Ketorolac tromethamine is largely metabolized in the liver. The metabolic products are hydroxylated and conjugated forms of the parent drug. The products of metabolism, and some unchanged drug, are excreted in the urine.

Clearance and Excretion

A single-dose study with 10 mg ketorolac tromethamine (n=9) demonstrated that the S-enantiomer is cleared approximately two times faster than the R-enantiomer, and that the clearance was independent of the route of administration. This means that the ratio of S/R plasma concentrations decreases with time after each dose. There is little or no inversion of the R- to S- form in humans. The clearance of the racemate in normal subjects, elderly individuals, and in hepatically and renally impaired patients, is outlined in Table 2.

The half-life of the ketorolac tromethamine S-enantiomer was approximately 2.5 hours (SD±0.4) compared with 5 hours (SD±1.7) for the R-enantiomer. In other studies, the half-life for the racemate has been reported to lie within the range of 5-6 hours.

Table 1 Table of Approximate Average Pharmacokinetic Parameters (Mean±SD) Following Oral, Intramuscular and Intravenous Doses of Ketorolac Tromethamine
		Oral †	Intramuscular*				Intravenous Bolus‡
Pharmacokinetic Parameters (units)		10 mg	15 mg	30 mg		60 mg	15 mg	30 mg
Bioavailability (extent)		100%
Tmax1 (min)		44±34	33±21**	44±29		33±21**	1.1±0.7**	2.9±1.8
Cmax2 (mcg/mL) [Single-dose]		0.87±0.22	1.14±0.32**	2.42±0.68		4.55±1.27**	2.47±0.51**	4.65±0.96
Cmax (mcg/mL) [steady state qid]		1.05±0.26**	1.56±0.44**	3.11±0.87**		N/A††	3.09±1.17**	6.85±2.61
Cmin3 (mcg/mL) [steady state qid]		0.29±0.07**	0.47±0.13**	0.93±0.26**		N/A	0.61±0.21**	1.04±0.35
Cavg4 (mcg/mL) [steady state qid]		0.59±0.2**	0.94±0.29**	1.88±0.59**		N/A	1.09±0.3**	2.17±0.59
Vβ5 (L/kg)		———— 0.175±0.039 ————					0.210±0.044
1Time-to-peak plasma concentration
2Peak plasma concentration
3Trough plasma concentration
4Average plasma concentration
5Volume of distribution
% Dose metabolized = <50	% Dose excreted in feces = 6
% Dose excreted in urine = 91	% Plasma protein binding = 99
†Derived from PO pharmacokinetic studies in 77 normal fasted volunteers
*Derived from IM pharmacokinetic studies in 54 normal volunteers
‡Derived from IV pharmacokinetic studies in 24 normal volunteers
††Not applicable because 60 mg is only recommended as a single dose
**Mean value was simulated from observed plasma concentration data and standard deviation was simulated from percent coefficient of variation for observed Cmax and Tmax data

Table 2 The Influence of Age, Liver and Kidney Function, on the Clearance and Terminal Half-life of Ketorolac Tromethamine (IM1 and ORAL2)
	Total Clearance [in L/h/kg]3			Terminal Half-life [in hours]
Type of Subjects	IM Mean (range)	ORAL Mean (range)		IM Mean (range)	ORAL Mean (range)
Normal Subjects IM (n=54) mean age=32, range=18-60 Oral (n=77) mean age=32, range=20-60	0.023 (0.010-0.046)	0.025 (0.013-0.050)		5.3 (3.5-9.2)	5.3 (2.4-9)
Healthy Elderly Subjects IM (n=13), Oral (n=12) mean age=72, range=65-78	0.019 (0.013-0.034)	0.024 (0.018-0.034)		7 (4.7-8.6)	6.1 (4.3-7.6)
Patients with Hepatic Dysfunction IM and Oral (n=7) mean age=51, range=43-64	0.029 (0.013-0.066)	0.033 (0.019-0.051)		5.4 (2.2-6.9)	4.5 (1.6-7.6)
Patients with Renal Impairment IM (n=25), Oral (n=9) serum creatinine=1.9-5.0 mg/dL, mean age (IM)=54, range=35-71 mean age (Oral)=57, range=39-70	0.015 (0.005-0.043)	0.016 (0.007-0.052)		10.3 (5.9-19.2)	10.8 (3.4-18.9)
Renal Dialysis Patients IM and Oral (n=9) mean age=40, range=27-63	0.016 (0.003-0.036)	−		13.6 (8.0-39.1)	−
1Estimated from 30 mg single IM doses of ketorolac tromethamine			IV-Administration: In normal subjects (n=37), the total clearance of 30 mg
2Estimated from 10 mg single oral doses of ketorolac tromethamine			IV-administered Ketorolac Tromethamine was 0.030 (0.017-0.051) L/h/kg.
3Liters/hour/kilogram			The terminal half-life was 5.6 (4.0-7.9) hours.

Accumulation

Ketorolac tromethamine administered as an IV bolus, every 6 hours, for 5 days, to healthy subjects (n=13), showed no significant difference in Cmax on Day 1 and Day 5. Trough levels averaged 0.29 mcg/mL (SD±0.13) on Day 1 and 0.55 mcg/mL (SD±0.23) on Day 6. Steady-state was approached after the fourth dose.

Accumulation of ketorolac tromethamine has not been studied in special populations (elderly patients, renal failure patients, or hepatic disease patients).

Kinetics in Special Populations

Elderly Patients

Based on single-dose data only, the half-life of the ketorolac tromethamine racemate increased from 5 to 7 hours in the elderly (65-78 years) compared with young healthy volunteers (24-35 years) (see Table 2). There was little difference in the Cmax for the two groups (elderly, 2.52 mcg/mL±0.77; young, 2.99 mcg/mL±1.03) (see PRECAUTIONS − Use in the Elderly).

Renally Impaired Patients

Based on single-dose data only, the mean half-life of ketorolac tromethamine in renally impaired patients is between 6 and 19 hours, and is dependent on the extent of the impairment. There is poor correlation between creatinine clearance and total ketorolac tromethamine clearance in the elderly and populations with renal impairment (r=0.5).

In patients with renal disease, the AUC∞ of each enantiomer increased by approximately 100% compared with healthy volunteers. The volume of distribution doubles for the S-enantiomer and increases by 1/5th for the R-enantiomer. The increase in volume of distribution of ketorolac tromethamine implies an increase in unbound fraction.

The AUC∞-ratio of the ketorolac tromethamine enantiomers in healthy subjects and patients remained similar, indicating there was no selective excretion of either enantiomer in patients compared to healthy subjects (see WARNINGS – Renal Effects).

Hepatic Effects

There was no significant difference in estimates of half-life, AUC∞, Cmax, in 7 patients with liver disease compared to healthy volunteers (see PRECAUTIONS – Hepatic Effects).

Clinical Studies

The analgesic efficacy of intramuscularly, intravenously and orally administered ketorolac tromethamine was investigated in two postoperative pain models: general surgery (orthopedic, gynecologic and abdominal) and oral surgery (removal of impacted third molars). The studies were double-blind, single- and multiple-dose, parallel trial designs, in patients with moderate to severe pain at baseline. Ketorolac tromethamine injection was compared as follows: IM to meperidine or morphine administered intramuscularly, and IV to morphine administered either directly IV or through a PCA (Patient-Controlled Analgesia) pump.

Short-term Use (up to 5 days) Studies

In the comparisons of intramuscular administration during the first hour, the onset of analgesic action was similar for ketorolac tromethamine and the narcotics, but the duration of analgesia was longer with ketorolac tromethamine than with the opioid comparators meperidine or morphine.

In a multi-dose, postoperative (general surgery) double-blind trial of ketorolac tromethamine 30 mg IM versus morphine 6 and 12 mg IM, each drug given on an “as needed” basis for up to 5 days, the overall analgesic effect of ketorolac tromethamine 30 mg IM was between that of morphine 6 and 12 mg. The majority of patients treated with either ketorolac tromethamine or morphine were dosed for up to 3 days; a small percentage of patients received 5 days of dosing.

In clinical settings where perioperative morphine was allowed, ketorolac tromethamine 30 mg IV, given once or twice as needed, provided analgesia comparable to morphine 4 mg IV once or twice as needed.

There was relatively limited experience with 5 consecutive days of ketorolac tromethamineIV use in controlled clinical trials, as most patients were given the drug for 3 days or less. The adverse events seen with IV-administered ketorolac tromethamine were similar to those observed with IM-administered ketorolac tromethamine, as would be expected based on the similar pharmacokinetics and bioequivalence (AUC, clearance, plasma half-life) of IV and IM routes of ketorolac tromethamine administration.

Clinical Studies with Concomitant Use of Opioids

Clinical studies in postoperative pain management have demonstrated that ketorolac tromethamine injection, when used in combination with opioids, significantly reduced opioid consumption. This combination may be useful in the subpopulation of patients especially prone to opioid-related complications. Ketorolac tromethamine and narcotics should not be administered in the same syringe.

In a postoperative study, where all patients received morphine by a PCA device, patients treated with ketorolac tromethamineIV as fixed intermittent boluses (e.g., 30 mg initial dose followed by 15 mg q3h), required significantly less morphine (26%) than the placebo group. Analgesia was significantly superior, at various postdosing pain assessment times, in the patients receiving ketorolac tromethamineIV plus PCA morphine as compared to patients receiving PCA-administered morphine alone.

Postmarketing Surveillance Study

A large postmarketing observational, non-randomized study, involving approximately 10,000 patients receiving ketorolac tromethamine, demonstrated that the risk of clinically serious gastrointestinal (G.I.) bleeding was dose-dependent (see Table 3A and 3B.) This was particularly true in elderly patients who received an average daily dose greater than 60 mg/day of ketorolac tromethamine (Table 3A).

Table 3
Incidence of Clinically Serious G.I. Bleeding as Related to Age, Total Daily Dose, and History of G.I. Perforation, Ulcer, Bleeding (PUB) after up to 5 Days of Treatment with Ketorolac Tromethamine Injection
A. Patients without History of PUB
Age of Patients	Total Daily Dose of Ketorolac Tromethamine Injection
	≤60 mg	>60 to 90 mg	>90 to 120 mg	>120 mg
<65 years of age	0.4%	0.4%	0.9%	4.6%
≥65 years of age	1.2%	2.8%	2.2%	7.7%
B. Patients with History of PUB
Age of Patients	Total Daily Dose of Ketorolac Tromethamine Injection
	≤60 mg	>60 to 90 mg	>90 to 120 mg	>120 mg
<65 years of age	2.1%	4.6%	7.8%	15.4%
≥65 years of age	4.7%	3.7%	2.8%	25%

Indications and Usage for Ketorolac Injection

Ketorolac tromethamine is indicated for the short-term (≤5 days) management of moderately severe, acute pain that requires analgesia at the opioid level, usually in a postoperative setting. Therapy should always be initiated with ketorolac tromethamine injection, and ketorolac tromethamine tablets are to be used only as continuation treatment, if necessary. Combined use of ketorolac tromethamine injection and tablets is not to exceed 5 days of use because of the potential of increasing the frequency and severity of adverse reactions associated with the recommended doses (see WARNINGS, PRECAUTIONS, DOSAGE AND ADMINISTRATION, and ADVERSE REACTIONS). Patients should be switched to alternative analgesics as soon as possible, but ketorolac tromethamine therapy is not to exceed 5 days.

Ketorolac tromethamine injection has been used concomitantly with morphine and meperidine, and has shown an opioid-sparing effect. For breakthrough pain, it is recommended to supplement the lower end of the ketorolac tromethamine injection dosage range with low doses of narcotics prn, unless otherwise contraindicated. Ketorolac tromethamine injection and narcotics should not be administered in the same syringe (see DOSAGE AND ADMINISTRATION − Pharmaceutical Information for Ketorolac tromethamine injection).

Contraindications

(see also Boxed WARNING)

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  Ketorolac tromethamine is CONTRAINDICATED in patients with active peptic ulcer disease, in patients with recent gastrointestinal bleeding or perforation, and in patients with a history of peptic ulcer disease or gastrointestinal bleeding.

  
  


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  Ketorolac tromethamine is CONTRAINDICATED in patients with advanced renal impairment, or in patients at risk for renal failure due to volume depletion (see WARNINGS for correction of volume depletion).

  
  


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  Ketorolac tromethamine is CONTRAINDICATED in labor and delivery because, through its prostaglandin synthesis inhibitory effect, it may adversely affect fetal circulation and inhibit uterine musculature, thus increasing the risk of uterine hemorrhage.

  
  


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  The use of ketorolac tromethamine is CONTRAINDICATED in nursing mothers because of the potential adverse effects of prostaglandin-inhibiting drugs on neonates.

  
  


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  Ketorolac tromethamine is CONTRAINDICATED in patients with previously demonstrated hypersensitivity to ketorolac tromethamine, or allergic manifestations to aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs).

  
  


• 
  

  Ketorolac tromethamine is CONTRAINDICATED as prophylactic analgesic before any major surgery, and is CONTRAINDICATED intra-operatively when hemostasis is critical because of the increased risk of bleeding.

  
  


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  Ketorolac tromethamine inhibits platelet function and is, therefore, CONTRAINDICATED in patients with suspected or confirmed cerebrovascular bleeding, hemorrhagic diathesis, incomplete hemostasis, and those at high risk of bleeding (see WARNINGS and PRECAUTIONS).

  
  


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  Ketorolac tromethamine is CONTRAINDICATED in patients currently receiving ASA or NSAIDs because of the cumulative risks of inducing serious NSAID related adverse events.

  
  


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  Ketorolac tromethamine injection is CONTRAINDICATED for neuraxial (epidural or intrathecal) administration due to its alcohol content.

  
  


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  The concomitant use of ketorolac tromethamine and probenecid is CONTRAINDICATED.

  
  

Warnings

(see also Boxed WARNING)

► The combined use of ketorolac tromethamine injection and tablets is not to exceed 5 days.

The most serious risks associated with ketorolac tromethamine are:

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  Gastrointestinal Ulcerations, Bleeding and Perforation: Ketorolac tromethamine is CONTRAINDICATED in patients with previously documented peptic ulcers and/or G.I. bleeding. Serious gastrointestinal toxicity, such as bleeding, ulceration, and perforation, can occur at any time, with or without warning symptoms, in patients treated with ketorolac tromethamine. Studies to date with NSAIDs have not identified any subset of patients not at risk of developing peptic ulceration and bleeding. Elderly or debilitated patients seem to tolerate ulceration or bleeding less well than other individuals, and most spontaneous reports of fatal G.I. events are in this population. Postmarketing experience with parenterally administered ketorolac tromethamine suggests that there may be a greater risk of gastrointestinal ulcerations, bleeding and perforation in the elderly.

  
  

  The incidence and severity of gastrointestinal complications increases with increasing dose of, and duration of treatment with ketorolac tromethamine. In a non-randomized, in-hospital postmarketing surveillance study, comparing parenteral ketorolac tromethamine to parenteral opioids, higher rates of clinically serious G.I. bleeding were seen in patients <65 years of age who received an average total daily dose of more than 90 mg of ketorolac tromethamine injection per day (see CLINICAL PHARMACOLOGY − Postmarketing Surveillance Study).

  
  

  The same study showed that elderly (≥65 years of age), and debilitated patients are more susceptible to gastrointestinal complications. A history of peptic ulcer disease was revealed as another risk factor that increases the possibility of developing serious gastrointestinal complications during ketorolac tromethamine therapy (see Tables 3A and B).

  
  


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  Impaired Renal Function: Ketorolac tromethamine should be used with caution in patients with impaired renal function, or a history of kidney disease because it is a potent inhibitor of prostaglandin synthesis. Renal toxicity with ketorolac tromethamine has been seen in patients with conditions leading to a reduction in blood volume and/or renal blood flow, where renal prostaglandins have a supportive role in the maintenance of renal perfusion. In these patients, administration of ketorolac tromethamine may cause a dose-dependent reduction in renal prostaglandin formation and may precipitate acute renal failure. Patients at greatest risk of this reaction are those with impaired renal function, dehydration, heart failure, liver dysfunction, those taking diuretics and the elderly. Discontinuation of ketorolac tromethamine therapy is usually followed by recovery to the pretreatment state.

  
  

Renal Effects: Ketorolac tromethamine and its metabolites are eliminated primarily by the kidneys, which, in patients with reduced creatinine clearance, will result in diminished clearance of the drug (see CLINICAL PHARMACOLOGY). Therefore, ketorolac tromethamine should be used with caution in patients with impaired renal function (see DOSAGE AND ADMINISTRATION) and such patients should be followed closely. With the use of ketorolac tromethamine, there have been reports of acute renal failure, nephritis, and nephrotic syndrome.

Because patients with underlying renal insufficiency are at increased risk of developing acute renal failure, the risks and benefits should be assessed prior to giving ketorolac tromethamine to these patients. Hence, in patients with moderately elevated serum creatinine, it is recommended that the daily dose of ketorolac tromethamine injection be reduced by half, not to exceed 60 mg/day. Ketorolac tromethamine is CONTRAINDICATED IN PATIENTS WITH SERUM CREATININE CONCENTRATIONS INDICATING ADVANCED RENAL IMPAIRMENT (see CONTRAINDICATIONS).

Hypovolemia should be corrected before treatment with ketorolac tromethamine is initiated.

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  Fluid Retention and Edema: Fluid retention, edema, retention of NaCl, oliguria, elevations of serum urea nitrogen and creatinine have been reported in clinical trials with ketorolac tromethamine. Therefore, ketorolac tromethamine should be used only very cautiously in patients with cardiac decompensation, hypertension, or similar conditions.

  
  


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  Hemorrhage: Because prostaglandins play an important role in hemostasis, and NSAIDs affect platelet aggregation as well, use of ketorolac tromethamine in patients who have coagulation disorders should be undertaken very cautiously, and those patients should be carefully monitored. Patients on therapeutic doses of anticoagulants (e.g., heparin or dicumarol derivatives) have an increased risk of bleeding complications if given ketorolac tromethamine concurrently; therefore, physicians should administer such concomitant therapy only extremely cautiously. The concurrent use of ketorolac tromethamine and prophylactic low-dose heparin (2500-5000 units q12h), warfarin and dextrans have not been studied extensively, but may also be associated with an increased risk of bleeding. Until data from such studies are available, physicians should carefully weigh the benefits against the risks, and use such concomitant therapy in these patients only extremely cautiously. In patients who receive anticoagulants for any reason, there is an increased risk of intramuscular hematoma formation from administered ketorolac tromethamine IM (see PRECAUTIONS − Drug Interactions). Patients receiving therapy that affects hemostasis should be monitored closely.

  
  

  In postmarking experience, postoperative hematomas and other signs of wound bleeding have been reported in association with the perioperative use of ketorolac tromethamine injection. Therefore, perioperative use of ketorolac tromethamine should be avoided and postoperative use be undertaken with caution when hemostasis is critical (see WARNINGS and PRECAUTIONS).

  
  


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  Anaphylactoid Reactions: Anaphylactoid reactions may occur in patients without a known previous exposure or hypersensitivity to aspirin, ketorolac tromethamine, or other NSAIDs, or in individuals with a history of angioedema, bronchospastic reactivity (e.g., asthma), and nasal polyps. Anaphylactoid reactions, like anaphylaxis, may have a fatal outcome.

  
  

Precautions

GENERAL

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  Hepatic Effects: Ketorolac tromethamine should be used with caution in patients with impaired hepatic function, or a history of liver disease. Treatment with ketorolac tromethamine may cause elevations of liver enzymes, and in patients with pre-existing liver dysfunction it may lead to the development of a more severe hepatic reaction. The administration of ketorolac tromethamine should be discontinued in patients in whom an abnormal liver test has occurred as a result of ketorolac tromethamine therapy.

  
  


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  Hematologic Effects: Ketorolac tromethamine inhibits platelet aggregation and may prolong bleeding time; therefore, it is contraindicated as a preoperative medication and caution should be used when hemostasis is critical. Unlike aspirin, the inhibition of platelet function by ketorolac tromethamine disappears within 24 to 48 hours after the drug is discontinued. Ketorolac tromethamine does not appear to affect platelet count, prothrombin time (PT) or partial thromboplastin time (PTT). In controlled clinical studies, where ketorolac tromethamine was administered intramuscularly or intravenously postoperatively, the incidence of clinically significant postoperative bleeding was 0.4% for ketorolac tromethamine compared to 0.2% in the control groups receiving narcotic analgesics.

  
  

INFORMATION FOR PATIENTS

Ketorolac tromethamine is a potent NSAID and may cause serious side effects such as gastrointestinal bleeding or kidney failure, which may result in hospitalization and even fatal outcome.

Physicians, when prescribing ketorolac tromethamine, should inform their patients of the potential risks of ketorolac tromethamine treatment (see Boxed WARNING, WARNINGS, PRECAUTIONS, and ADVERSE REACTIONS sections). Advise patients not to give ketorolac tromethamine tablets to other family members and to discard any unused drug.

Remember that the total duration of ketorolac tromethamine therapy is not to exceed 5 (five) days.

DRUG INTERACTIONS

Ketorolac is highly bound to human plasma protein (mean 99.2%).

The in vitro binding of warfarin to plasma proteins is only slightly reduced by ketorolac tromethamine (99.5% control vs 99.3%) when ketorolac plasma concentrations reach 5 to 10 mcg/mL. Ketorolac does not alter digoxin protein binding. In vitro studies indicate that, at therapeutic concentrations of salicylate (300 mcg/mL), the binding of ketorolac was reduced from approximately 99.2% to 97.5%, representing a potential two-fold increase in unbound ketorolac plasma levels. Therapeutic concentrations of digoxin, warfarin, ibuprofen, naproxen, piroxicam, acetaminophen, phenytoin, and tolbutamide did not alter ketorolac tromethamine protein binding.

In a study involving 12 volunteers, ketorolac tromethamine tablets were co-administered with a single dose of 25 mg warfarin, causing no significant changes in pharmacokinetics or pharmacodynamics of warfarin. In another study, ketorolac tromethamine injection was given with two doses of 5000 U of heparin to 11 healthy volunteers, resulting in a mean template bleeding time of 6.4 minutes (3.2-11.4 min) compared to a mean of 6.0 minutes (3.4-7.5 min) for heparin alone and 5.1 minutes (3.5-8.5 min) for placebo. Although these results do not indicate a significant interaction between ketorolac tromethamine and warfarin or heparin, the administration of ketorolac tromethamine to patients taking anticoagulants should be done extremely cautiously and patients should be closely monitored (see WARNINGS and PRECAUTIONS).

Ketorolac tromethamine injection reduced the diuretic response to furosemide in normo-volemic healthy subjects by approximately 20% (mean sodium and urinary output decreased 17%).

Concomitant administration of ketorolac tromethamine tablets and probenecid resulted in decreased clearance of ketorolac and significant increases in ketorolac plasma levels (total AUC increased approximately 3-fold from 5.4 to 17.8 mcg/h/mL) and terminal half-life increased approximately 2-fold from 6.6 to 15.1 hours. Therefore, concomitant use of ketorolac tromethamine and probenecid is contraindicated.

Inhibition of renal lithium clearance, leading to an increase in plasma lithium concentration, has been reported with some prostaglandin synthesis-inhibiting drugs. The effect of ketorolac tromethamine on plasma lithium has not been studied, but cases of increased lithium plasma levels during ketorolac tromethamine therapy have been reported.

Concomitant administration of methotrexate and some NSAIDs has been reported to reduce the clearance of methotrexate, enhancing the toxicity of methotrexate. The effect of ketorolac tromethamine on methotrexate clearance has not been studied.

In postmarketing experience, there have been reports of a possible interaction between ketorolac tromethamine injection and non-depolarizing muscle relaxants that resulted in apnea. The concurrent use of ketorolac tromethamine with muscle relaxants has not been formally studied.

Concomitant use of ACE inhibitors may increase the risk of renal impairment, particularly in volume depleted patients.

Sporadic cases of seizures have been reported during concomitant use of ketorolac tromethamine and antiepileptic drugs (phenytoin, carbamazepine).

Hallucinations have been reported when ketorolac tromethamine was used in patients taking psychoactive drugs (fluoxetine, thiothixene, alprazolam).

Ketorolac tromethamine injection has been administered concurrently with morphine in several clinical trials of postoperative pain without evidence of adverse interactions. Do not mix ketorolac tromethamine and morphine in the same syringe.

There is no evidence, in animal or human studies, that ketorolac tromethamine induces or inhibits hepatic enzymes capable of metabolizing itself or other drugs.

Carcinogenesis, Mutagenesis, and Impairment of Fertility

An 18-month study in mice with ketorolac tromethamine tablets at 2 mg/kg/day (0.9 times the human systemic exposure at the recommended IM or IV dose of 30 mg qid, based on area-under-the-plasma concentration curve [AUC]), and a 24-month study in rats at 5 mg/kg/day (0.5 times the human AUC), showed no evidence of tumorigenicity.

Ketorolac tromethamine was not mutagenic in the Ames test, unscheduled DNA synthesis and repair, and in forward mutation assays. Ketorolac tromethamine did not cause chromosome breakage in the in vivo mouse micronucleus assay. At 1590 mcg/mL and at higher concentrations, ketorolac tromethamine increased the incidence of chromosomal aberrations in Chinese hamster ovarian cells.

Impairment of fertility did not occur in male or female rats at oral doses of 9 mg/kg (0.9 times the human AUC) and 16 mg/kg (1.6 times the human AUC) of ketorolac tromethamine, respectively.

Pregnancy

Pregnancy Category C. Reproduction studies have been performed during organogenesis, using daily doses of ketorolac tromethamine tablets at 3.6 mg/kg (0.37 times the human AUC) in rabbits and at 10 mg/kg (1 times the human AUC) in rats. Results of these studies did not reveal evidence of teratogenicity to the fetus. Doses of ketorolac tromethamine tablets at 1.5 mg/kg (0.14 times the human AUC), administered after gestation day 17, caused dystocia and higher pup mortality in rats. There are no adequate and well-controlled studies of ketorolac tromethamine in pregnant women. Ketorolac tromethamine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Labor and Delivery

The use of ketorolac tromethamine is contraindicated in labor and delivery because, through its prostaglandin synthesis inhibitory effect, it may adversely affect fetal circulation and inhibit uterine musculature, thus increasing the risk of uterine hemorrhage (see CONTRAINDICATIONS).

Lactation and Nursing

After a single administration of a 10 mg ketorolac tromethamine tablet to humans, the maximum milk concentration observed was 7.3 ng/mL and the maximum milk-to-plasma ratio was 0.037. After one day of dosing (qid), the maximum milk concentration was 7.9 ng/mL and the maximum milk-to-plasma ratio was 0.025. Because of the possible adverse effects of prostaglandin-inhibiting drugs on neonates, use in nursing mothers is CONTRAINDICATED.

Pediatric Use

Safety and efficacy in pediatric patients (less than 16 years of age) have not been established. Therefore, use of ketorolac tromethamine in pediatric patients is not

Nexiclon XR

Pronunciation: KLOE-ni-deen
Generic Name: Clonidine
Brand Name: Nexiclon XR

Nexiclon XR is used for:

Treating high blood pressure. It may be used alone or with other medicines. It may also be used for other conditions as determined by your doctor.

Nexiclon XR is an alpha agonist. It works by relaxing blood vessels and decreasing heart rate, which lowers blood pressure.

Do NOT use Nexiclon XR if:

• you are allergic to any ingredient in Nexiclon XR

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

Before using Nexiclon XR:

Some medical conditions may interact with Nexiclon XR. 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 had a skin reaction to the patch form of Nexiclon XR


• if you have kidney problems, heart problems (eg, irregular heartbeat), problems with the blood vessels in your heart or brain, or the blood disease porphyria


• if you will be having surgery


• if you have a history of a stroke or a recent heart attack


• if you are taking another medicine that contains clonidine

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

• Beta-blockers (eg, propranolol) because severe and sometimes life-threatening increased blood pressure may occur if Nexiclon XR is suddenly stopped


• Calcium channel blockers (eg, verapamil) or digoxin because they may increase the risk of Nexiclon XR's side effects, including slow or irregular heartbeat


• Tricyclic antidepressants (eg, amitriptyline) because they may decrease Nexiclon XR's effectiveness


• Barbiturates (eg, phenobarbital) because the risk of their side effects may be increased by Nexiclon XR

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

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

• Take Nexiclon XR by mouth with or without food.


• Shake well for 5 to 10 seconds before each use.


• Use the measuring device that comes with Nexiclon XR to measure your dose. Ask your pharmacist for help if you are unsure of how to measure your dose.


• Insert the adapter into the neck of the bottle. Insert the syringe tip into the adapter and turn the bottle over. Draw out the prescribed amount of Nexiclon XR.


• Nexiclon XR works best if it is taken at the same time each day, preferably at bedtime unless your doctor tells you differently.


• Continue to take Nexiclon XR even if you feel well. Do not miss any doses.


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

Ask your health care provider any questions you may have about how to use Nexiclon XR.

Important safety information:

• Nexiclon XR may cause drowsiness, dizziness, lightheadedness, or blurred vision. These effects may be worse if you take it with alcohol or certain medicines. Use Nexiclon XR with caution. Do not drive or perform other possibly unsafe tasks until you know how you react to it.


• Nexiclon XR may cause dizziness, lightheadedness, or fainting; alcohol, hot weather, exercise, or fever may increase these effects. To prevent them, sit up or stand slowly, especially in the morning. Sit or lie down at the first sign of any of these effects.


• Talk to your doctor before using alcohol or medicines that may cause drowsiness (eg, sleep aids, muscle relaxers) while you are using Nexiclon XR; it may add to their effects. Ask your pharmacist if you have questions about which medicines may cause drowsiness.


• Do NOT take more than the recommended dose without checking with your doctor.


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


• Patients who take medicine for high blood pressure often feel tired or run down for a few weeks after starting treatment. Be sure to take your medicine even if you may not feel "normal." Tell your doctor if you develop any new symptoms.


• If you have high blood pressure, do not use nonprescription products that contain stimulants. These products may include diet pills or cold medicines. Contact your doctor if you have any questions or concerns.


• If you experience dry mouth, use sugarless candy or gum, or melt bits of ice in your mouth to help keep your mouth moist.


• Do not suddenly stop taking Nexiclon XR without talking to your doctor. Nervousness, agitation, confusion, tremor, and headache may occur. These may be followed by a rapid, severe rise in blood pressure. You may be at greater risk if you use high doses or if you also take a beta-blocker (eg, propranolol). If you need to stop taking Nexiclon XR, follow your doctor's instructions for slowly decreasing your dose.


• Contact your doctor if you develop an illness that includes vomiting or if you vomit soon after you take Nexiclon XR.


• Lab tests, including blood pressure, may be performed while you take Nexiclon XR. These tests may be used to monitor your condition or check for side effects. Be sure to keep all doctor and lab appointments.


• Use Nexiclon XR with caution in the ELDERLY; they may be more sensitive to its effects, especially dizziness.


• Nexiclon XR should be used with extreme caution in CHILDREN; safety and effectiveness in children have not been confirmed. Children may be more sensitive to withdrawal symptoms after suddenly stopping Nexiclon XR.


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

If you suddenly stop taking Nexiclon XR, you may experience WITHDRAWAL symptoms, including nervousness, agitation, headache, tremor, and rapid increase in blood pressure. Do not suddenly stop taking Nexiclon XR without checking with your doctor.

Possible side effects of Nexiclon XR:

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:

Constipation; dizziness; drowsiness; dry mouth; headache; nausea; tiredness; trouble sleeping.

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; unusual hoarseness); blurred vision or other vision changes; chest pain; decreased sexual desire or ability; fainting; fast, slow, or irregular heartbeat; hallucinations; mental or mood changes (eg, anxiety, agitation, depression, nervousness, restlessness); severe or persistent headache or dizziness; shortness of breath; swelling of the hands, ankles, or feet; unusual bruising or bleeding.

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: Nexiclon XR 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 coma; decreased body temperature (feeling very cold); decreased reflexes; difficult or slow breathing; fainting; irritability; pinpoint pupils; seizures; severe or persistent dizziness, headache, or drowsiness; slow or irregular heartbeat; weakness.

Proper storage of Nexiclon XR:

Store Nexiclon XR at 77 degrees F (25 degrees C). Brief storage at temperatures between 59 and 86 degrees F (15 and 30 degrees C) is permitted. Do not store in the bathroom. Store away from heat, moisture, and light. Keep Nexiclon XR out of the reach of children and away from pets.

General information:

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


• Nexiclon XR 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 Nexiclon XR. 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 Nexiclon XR resources

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

Compare Nexiclon XR with other medications

• High Blood Pressure

Sulfacetamide/Urea Lotion

Pronunciation: sul-fa-SEE-ta-mide/yoor-EE-a
Generic Name: Sulfacetamide/Urea
Brand Name: Carmol Scalp Treatment

Sulfacetamide/Urea Lotion is used for:

Treating certain skin conditions (eg, seborrheic dermatitis), dandruff, and certain bacterial infections of the skin. It may also be used for other conditions as determined by your doctor.

Sulfacetamide/Urea Lotion is a sulfonamide antibiotic. It works by killing bacteria, helping to shed scaly skin, and softening the skin.

Do NOT use Sulfacetamide/Urea Lotion if:

• you are allergic to any ingredient in Sulfacetamide/Urea Lotion


• you have had a severe allergic reaction (eg, severe rash, hives, difficulty breathing, dizziness) to any other sulfonamide medicine, such as acetazolamide, celecoxib, certain diuretics (eg, hydrochlorothiazide), glyburide, probenecid, sulfamethoxazole, valdecoxib, or zonisamide


• you are taking methenamine

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

Before using Sulfacetamide/Urea Lotion:

Some medical conditions may interact with Sulfacetamide/Urea Lotion. 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 a history of lupus

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

• Silver-containing products (eg, silver sulfadiazine) because they may decrease Sulfacetamide/Urea Lotion's effectiveness


• Methenamine because it may increase the risk of Sulfacetamide/Urea Lotion's side effects

This may not be a complete list of all interactions that may occur. Ask your health care provider if Sulfacetamide/Urea Lotion 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 Sulfacetamide/Urea Lotion:

Use Sulfacetamide/Urea Lotion as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Sulfacetamide/Urea Lotion is for use on the skin only. Wash your hands before and immediately after using Sulfacetamide/Urea Lotion. Clean the affected area before applying Sulfacetamide/Urea Lotion. Apply a thin film of medicine to the affected areas as directed.


• To clear up your infection completely, use Sulfacetamide/Urea Lotion for the full course of treatment. Keep using it even if you feel better in a few days.


• Sulfacetamide/Urea Lotion works best if it is used at the same time each day.


• Continue to use Sulfacetamide/Urea Lotion even if you feel well. Do not miss any doses.


• If you miss a dose of Sulfacetamide/Urea Lotion, 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 Sulfacetamide/Urea Lotion.

Important safety information:

• It may take several days for Sulfacetamide/Urea Lotion to work fully.


• Avoid getting Sulfacetamide/Urea Lotion in your eyes, nose, or mouth.


• Talk with your doctor before you use any other medicines or cleansers on your skin.


• Contact your doctor right away if stomach pain or cramps, severe diarrhea, or bloody stools occur. Do not treat diarrhea without first checking with your doctor.


• Sulfacetamide/Urea Lotion only works against bacteria; it does not treat viral infections.


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


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


• Sulfacetamide/Urea Lotion 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 Sulfacetamide/Urea Lotion while you are pregnant. It is not known if Sulfacetamide/Urea Lotion is found in breast milk after topical use. If you are or will be breast-feeding while you use Sulfacetamide/Urea Lotion, check with your doctor. Discuss any possible risks to your baby.

Possible side effects of Sulfacetamide/Urea Lotion:

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:

Irritation, stinging, or burning of the skin.

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

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); bloody diarrhea; fever; joint pain; red, swollen, or blistered skin; severe diarrhea; sores in the mouth; stomach cramps/pain.

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

If OVERDOSE is suspected:

Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately. Sulfacetamide/Urea Lotion may be harmful if swallowed. Symptoms of ingestion may include change in the amount of urine; nausea; vomiting.

Proper storage of Sulfacetamide/Urea Lotion:

Store Sulfacetamide/Urea Lotion at room temperature, between 59 and 86 degrees F (15 and 30 degrees C). Store away from heat, moisture, and light. Do not store in the bathroom. Do not freeze. Keep Sulfacetamide/Urea Lotion out of the reach of children and away from pets.

General information:

• If you have any questions about Sulfacetamide/Urea Lotion, please talk with your doctor, pharmacist, or other health care provider.


• Sulfacetamide/Urea Lotion 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 Sulfacetamide/Urea Lotion. 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 Sulfacetamide/Urea resources

• Sulfacetamide/Urea Use in Pregnancy & Breastfeeding
• Sulfacetamide/Urea Support Group
• 0 Reviews for Sulfacetamide/Urea - Add your own review/rating

Compare Sulfacetamide/Urea with other medications

• Dandruff
• Seborrheic Dermatitis
• Secondary Cutaneous Bacterial Infections

Nucynta ER

Generic Name: tapentadol (Oral route)

ta-PEN-ta-dol

Oral route(Tablet, Extended Release)

Tapentadol extended-release contains tapentadol, a mu-opioid agonist and Schedule II controlled substance, with risk of misuse, abuse, and diversion similar to other opioid analgesics. Tapentadol extended-release is not intended for use as an as-needed analgesic or for the management of acute or postoperative pain. Tapentadol extended-release tablets should be swallowed whole. Taking split, broken, chewed, dissolved, or crushed tapentadol extended-release tablets could lead to rapid release and absorption of a potentially fatal dose of tapentadol. Patients must not consume alcoholic beverages, prescription or non-prescription medications containing alcohol. Co-ingestion of alcohol with tapentadol extended-release may result in a potentially fatal overdose of tapentadol .

Commonly used brand name(s)

In the U.S.

• Nucynta


• Nucynta ER

Available Dosage Forms:

• Tablet


• Tablet, Extended Release

Therapeutic Class: Analgesic

Chemical Class: Opioid

Uses For Nucynta ER

Tapentadol is a narcotic analgesic that acts in the central nervous system to relieve moderate or severe pain. If tapentadol is used for a long time, it may become habit-forming (causing mental or physical dependence). Physical dependence may lead to side effects when you stop taking the medicine. Since this medicine is only used for short-term relief of pain, physical dependence will probably not occur.

This medicine is available only with your doctor's prescription.

Before Using Nucynta ER

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

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

Pediatric

Appropriate studies have not been performed on the relationship of age to the effects of tapentadol in the pediatric population. Safety and efficacy have not been established.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of tapentadol in the elderly. However, elderly patients are more likely to have age-related liver or kidney problems, which may require an adjustment in the dose for patients receiving tapentadol.

Pregnancy

	Pregnancy Category	Explanation
All Trimesters	C	Animal studies have shown an adverse effect and there are no adequate studies in pregnant women OR no animal studies have been conducted and there are no adequate studies in pregnant women.

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Brofaromine


• Clorgyline


• Furazolidone


• Iproniazid


• Isocarboxazid


• Lazabemide


• Linezolid


• Moclobemide


• Nialamide


• Pargyline


• Phenelzine


• Procarbazine


• Rasagiline


• Selegiline


• Toloxatone


• Tranylcypromine

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Alfentanil


• Almotriptan


• Alprazolam


• Amitriptyline


• Amoxapine


• Anileridine


• Buprenorphine


• Buspirone


• Butabarbital


• Butorphanol


• Chlordiazepoxide


• Chlorpromazine


• Citalopram


• Clomipramine


• Clonazepam


• Clorazepate


• Codeine


• Desipramine


• Desvenlafaxine


• Dexmedetomidine


• Dezocine


• Diazepam


• Difenoxin


• Dihydrocodeine


• Diphenhydramine


• Diphenoxylate


• Dothiepin


• Doxepin


• Doxylamine


• Duloxetine


• Eletriptan


• Escitalopram


• Estazolam


• Eszopiclone


• Ethchlorvynol


• Fentanyl


• Flumazenil


• Fluoxetine


• Fluphenazine


• Flurazepam


• Fluvoxamine


• Frovatriptan


• Halazepam


• Hydrocodone


• Hydromorphone


• Hydroxyzine


• Imipramine


• Levomethadyl


• Levorphanol


• Lofepramine


• Lorazepam


• Meperidine


• Meprobamate


• Methadone


• Midazolam


• Milnacipran


• Morphine


• Morphine Sulfate Liposome


• Nalbuphine


• Naratriptan


• Nefazodone


• Nortriptyline


• Oxazepam


• Oxycodone


• Oxymorphone


• Paroxetine


• Pentazocine


• Pentobarbital


• Perphenazine


• Phenobarbital


• Prazepam


• Prochlorperazine


• Promethazine


• Propofol


• Propoxyphene


• Protriptyline


• Quazepam


• Ramelteon


• Remifentanil


• Rizatriptan


• Secobarbital


• Sertraline


• Sufentanil


• Sumatriptan


• Temazepam


• Thioridazine


• Tramadol


• Triazolam


• Trifluoperazine


• Trimipramine


• Venlafaxine


• Zaleplon


• Zolmitriptan


• Zolpidem

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following is usually not recommended, but may be unavoidable in some cases. If used together, your doctor may change the dose or how often you use this medicine, or give you special instructions about the use of food, alcohol, or tobacco.

• Ethanol

Other Medical Problems

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

• Alcohol abuse, history of or


• Drug abuse or dependence, history of—Physical dependence on tapentadol may be more likely to develop.

• Bowel blockage (e.g., paralytic ileus) or


• Kidney disease, severe or


• Liver disease, severe or


• Lung disease (e.g., asthma or hypercapnia), severe—Should not be used in patients with these conditions.

• Brain tumor or head injury, history of or


• Breathing or other lung problems (e.g., chronic obstructive pulmonary disease [COPD], hypoxia, or sleep apnea) or


• Depression, history of or


• Gallbladder problems or


• Kyphoscoliosis (severe curvature of the spine that can cause breathing problems) or


• Pancreatitis (inflammation of the pancreas) or


• Seizures or epilepsy, history of or


• Underactive thyroid—Use with caution. May make these conditions worse.

• Liver disease—Use with caution. The effects may be increased because of slower removal from the body.

Proper Use of tapentadol

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

Take this medicine only as directed by your doctor. Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered. To do so may increase the chance of side effects and the chances of abuse.

This medicine should come with a Medication Guide. Read and follow these instructions carefully. Ask your doctor if you have any questions.

You may take this medicine with or without food.

• For oral dosage form (tablets):
  
  • For pain:
    
    • Adults—50 to 100 milligrams (mg) every 4 to 6 hours. Your doctor may adjust your dose if needed.
    
    
    • Children—Use and dose must be determined by your doctor.
    
    
  
  

Missed Dose

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

Storage

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

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Precautions While Using Nucynta ER

It is very important that your doctor check your progress at regular visits to make sure the medicine is working properly and to check for any unwanted effects.

You should not use this medicine if you have used an MAO inhibitor (MAOI) such as isocarboxazid, phenelzine, selegiline, tranylcypromine, Eldepryl®, Marplan®, Nardil®, or Parnate® within the past 14 days.

This medicine will add to the effects of alcohol and other central nervous system (CNS) depressants. CNS depressants are medicines that slow down the nervous system and may cause drowsiness. Some examples of CNS depressants are antihistamines or medicines for hay fever or colds; sedatives, tranquilizers, or sleeping medicine; prescription pain medicines including other narcotics; barbiturates; medicines for seizures; muscle relaxants; or anesthetics, including some dental anesthetics. Do not drink alcoholic beverages, and check with your doctor before taking any of these medicines while you are using tapentadol.

This medicine may cause some people to become dizzy, lightheaded, faint, drowsy, or less alert than they are normally. Make sure you know how you react to this medicine before you drive, use machines, or do anything else that could be dangerous if you are dizzy or not alert. Getting up slowly from a lying or sitting position may also help.

Make sure your doctor knows about all the other medicines you are using. This medicine may cause a serious condition called serotonin syndrome. This is more likely to occur when it is taken with certain medicines for depression (e.g., amitriptyline, doxepin, fluoxetine, nortriptyline, paroxetine, Celexa®, Effexor®, Elavil®, Lexapro™, Pamelor®, Paxil®, Sinequan®, or Zoloft®), pain (e.g., tramadol [e.g., Ultram®]), or migraine headaches (sumatriptan [e.g., Imitrex®], zolmitriptan [e.g., Zomig®], or rizatriptan [e.g., Maxalt®]). Check with your doctor first before taking any other medicines.

Do not stop taking this medicine without first checking with your doctor. Your doctor may want you to gradually reduce the amount you are using before stopping it completely. This may help prevent a possible worsening of your condition and reduce the possibility of withdrawal symptoms such as anxiety, diarrhea, headache, nausea, shivering, sweating, tremors, or trouble with sleeping.

Nucynta ER Side Effects

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

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

Less common

• Bladder pain


• bloody or cloudy urine


• body aches or pain


• chills


• cough


• difficult, burning, or painful urination


• difficulty in breathing


• ear congestion


• fever


• frequent urge to urinate


• headache


• loss of voice


• lower back or side pain


• muscle aches


• nasal congestion


• runny nose


• sneezing


• sore throat


• stuffy or runny nose


• unusual tiredness or weakness

Rare

• Anxiety


• being forgetful


• burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings


• changes in patterns and rhythms of speech


• clumsiness or unsteadiness


• confusion


• confusion about identity, place, and time


• convulsions


• delusions


• dementia


• drowsiness


• dry mouth


• fainting


• false or unusual sense of well-being


• fast heartbeat


• feeling drunk


• hives


• hoarseness


• hyperventilation


• irregular heartbeats


• irregular, fast, slow, or shallow breathing


• irritability


• itching


• joint pain, stiffness, or swelling


• nervousness


• pale or blue lips, fingernails, or skin


• rash


• redness of the skin


• relaxed and calm


• restlessness


• sensation of heaviness


• shakiness and unsteady walk


• shortness of breath


• sleepiness


• slurred speech


• swelling


• swelling of the eyelids, face, lips, hands, or feet


• tightness in the chest


• trouble in speaking


• trouble with sleeping


• troubled breathing or swallowing


• unsteadiness, trembling, or other problems with muscle control or coordination


• wheezing

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

More common

• Constipation


• dizziness


• nausea


• sleepiness or unusual drowsiness


• vomiting

Less common

• Abnormal dreams


• acid or sour stomach


• belching


• decreased appetite


• difficulty in moving


• feeling hot


• feeling of warmth


• heartburn


• increased sweating


• indigestion


• muscle pain or stiffness


• rash


• redness of the face, neck, arms, and occasionally, upper chest


• sleeplessness


• stomach discomfort, upset, or pain


• sudden sweating


• unable to sleep


• unusual drowsiness, dullness, tiredness, weakness, or feeling of sluggishness

Rare

• Blurred or loss of vision


• disturbed color perception


• double vision


• halos around lights


• night blindness


• overbright appearance of lights


• tunnel vision

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

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

See also: Nucynta ER side effects (in more detail)

The information contained in the Thomson Reuters Micromedex products as delivered by Drugs.com is intended as an educational aid only. It is not intended as medical advice for individual conditions or treatment. It is not a substitute for a medical exam, nor does it replace the need for services provided by medical professionals. Talk to your doctor, nurse or pharmacist before taking any prescription or over the counter drugs (including any herbal medicines or supplements) or following any treatment or regimen. Only your doctor, nurse, or pharmacist can provide you with advice on what is safe and effective for you.

The use of the Thomson Reuters Healthcare products is at your sole risk. These products are provided "AS IS" and "as available" for use, without warranties of any kind, either express or implied. Thomson Reuters Healthcare and Drugs.com make no representation or warranty as to the accuracy, reliability, timeliness, usefulness or completeness of any of the information contained in the products. Additionally, THOMSON REUTERS HEALTHCARE MAKES NO REPRESENTATION OR WARRANTIES AS TO THE OPINIONS OR OTHER SERVICE OR DATA YOU MAY ACCESS, DOWNLOAD OR USE AS A RESULT OF USE OF THE THOMSON REUTERS HEALTHCARE PRODUCTS. ALL IMPLIED WARRANTIES OF MERCHANTABILITY AND FITNESS FOR A PARTICULAR PURPOSE OR USE ARE HEREBY EXCLUDED. Thomson Reuters Healthcare does not assume any responsibility or risk for your use of the Thomson Reuters Healthcare products.

More Nucynta ER resources

• Nucynta ER Side Effects (in more detail)
• Nucynta ER Use in Pregnancy & Breastfeeding
• Nucynta ER Drug Interactions
• 3 Reviews for Nucynta ER - Add your own review/rating

• Nucynta ER Extended-Release Tablets MedFacts Consumer Leaflet (Wolters Kluwer)


• Nucynta ER Prescribing Information (FDA)


• Tapentadol Professional Patient Advice (Wolters Kluwer)


• Nucynta Prescribing Information (FDA)


• Nucynta Monograph (AHFS DI)


• Nucynta MedFacts Consumer Leaflet (Wolters Kluwer)


• Nucynta Consumer Overview

Compare Nucynta ER with other medications

• Pain

Topicort LP Cream

Pronunciation: dess-OX-ee-MET-ah-sone
Generic Name: Desoximetasone
Brand Name: Examples include Topicort and Topicort LP

Topicort LP Cream is used for:

Relieving inflammation and itching of the skin.

Topicort LP Cream is a topical adrenocortical steroid. The precise way it works is unclear, but it is thought to reduce skin inflammation (redness, swelling, itching, and irritation) by stopping the production of certain chemicals in the body.

Do NOT use Topicort LP Cream if:

• you are allergic to any ingredient in Topicort LP Cream

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

Before using Topicort LP Cream:

Some medical conditions may interact with Topicort LP 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, foods, or other substances


• if you have a skin infection, measles, thinning of the skin, tuberculosis (TB), chicken pox, shingles, a positive TB skin test, or have recently had a vaccination

Some MEDICINES MAY INTERACT with Topicort LP Cream. Because little, if any, of Topicort LP Cream is absorbed into the blood, the risk of it interacting with another medicine is low.

Ask your health care provider if Topicort LP 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 Topicort LP Cream:

Use Topicort LP 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(s). Gently rub the medicine in until it is evenly distributed. Wash your hands after applying the medicine, unless your hands are part of the treated area.


• Do not cover the treated area(s) with bandages or other dressings unless advised to do so by your health care provider.


• If you miss a dose of Topicort LP Cream, 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 Topicort LP Cream.

Important safety information:

• Topicort LP Cream is for external use only. Avoid contact with eyes and other mucous membranes (nostrils, mouth). If Topicort LP Cream gets in your eyes, flush them with cool tap water immediately.


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


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


• If Topicort LP Cream was prescribed to treat the diaper area of a child, avoid using tight-fitting diapers or plastic pants.


• Corticosteroids may affect growth rate in CHILDREN and teenagers in some cases. They may need regular growth checks while they use Topicort LP Cream.


• Topicort LP Cream should be used with extreme caution in CHILDREN; safety and effectiveness in 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 Topicort LP Cream while you are pregnant. It is not known if Topicort LP Cream is found in breast milk. If you are or will be breast-feeding while you use Topicort LP Cream, check with your doctor. Discuss any possible risks to your baby.

Possible side effects of Topicort LP 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:

Mild, temporary stinging when first applied.

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); itching, burning, redness, or swelling not present before using Topicort LP Cream.

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: Topicort LP 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. Topicort LP Cream may be harmful if swallowed.

Proper storage of Topicort LP Cream:

Store Topicort LP Cream at room temperature, between 59 and 86 degrees F (15 and 30 degrees C). Store away from heat, moisture, and light. Do not store in the bathroom. Keep Topicort LP Cream out of the reach of children and away from pets.

General information:

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


• Topicort LP 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 Topicort LP 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 Topicort LP resources

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

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