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(Posted: 1/17/2003)
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Statement
AGENERASE (amprenavir) Capsules & Oral Solution
[October 2, 2002:GlaxoSmithKline]
[Other labeling changes not in 2002 PDR: http://www.fda.gov/medwatch/SAFETY/2002/feb02.htm#agener,
http://www.fda.gov/medwatch/SAFETY/2002/aug02.htm#agener ]
Labeling provides for a change in the Carcinogenesis and Mutagenesis section of the AGENERASE (amprenavir) product labeling based on the results of a two-year carcinogenicity studies in mice and rats.
Also, revisions to the labeling provide for the inclusion of information regarding co-administration of AGENERASE (amprenavir) with delavirdine.
Contact the company for a copy of the new labeling/package insert.
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[October 25, 2002:Abbott]
[Other labeling changes not in 2002 PDR: http://www.fda.gov/medwatch/SAFETY/2002/aug02.htm#aminos ]
Aminosyn 5%, 7%, 8.5%, 8.5% w/Electrolytes & 10%
Aminosyn 3.5%, 3.5% M and 7% w/ Electrolytes
Aminosyn-RF 5.2%
Aminosyn-HBC 7%
Aminosyn-PF 7%
Aminosyn-II w/Electrolytes
Aminosyn II
Aminosyn-PF 10%
DESCRIPTION: Section modified to reflect multiple reformulations, listed above. Contact the company for a copy of the new labeling/package insert.
All Labels
WARNINGS:
Warning: This product contains aluminum that may be toxic. Aluminum may reach toxic levels with prolonged parenteral administration if kidney function is impaired. Premature neonates are particularly at risk because their kidneys are immature, and they require large amounts of calcium and phosphorous solutions, which contain aluminum.
Research indicates that patients with impaired kidney function, including premature neonates, who receive parenteral levels of aluminum at greater than 4 to 5mcg/kg/day accumulate aluminum at levels associated with central nervous system and bone toxicity. Tissue loading may occur at even lower rates of administration.
PRECAUTIONS:
This product contains no more than 25 mcg/L of aluminum.
All labels except Aminosyn RF 5.2% 500 Ml
The flexible plastic container is fabricated from a specially formulated polyvinylchloride. Water can permeate from inside the container into the overwrap but not in amounts sufficient to affect the solution significantly.
Solutions in contact with the plastic container may leach out certain chemical components from the plastic in very small amounts; however, biological testing was supportive of the safety of the plastic container materials.
Exposure to temperatures above 25 0 C/77 0 F during transport and storage will lead to minor losses in moisture content. Higher temperatures lead to greater losses. It is unlikely that these minor losses will lead to clinically significant changes within the expiration period.
All Labels
WARNINGS: The following paragraph is deleted due to the reformulation.
[Aminosyn products] contain potassium metabisulfite or sodium hydrosulfite, sulfites that may cause allergic-type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people. The overall prevalence of sulfite sensitivity in the general population is unknown and probably low. Sulfite sensitivity is seen more frequently in asthmatic than in nonasthmatic people.
DOSAGE AND ADMINISTRATION:
WARNING: Do not use flexible container in series connections.
Aminosyn HBC 7% 500 and 1000 mL
Aminosyn PF 7% 500 mL
PRECAUTIONS:
Added as 7th paragraph:
Essential fatty acid deficiency (EFAD) is becoming increasingly recognized in patients on long-term TPN (more than 5 days). The use of fat emulsion to provide 4 – 10% of total caloric intake as linoleic acid may prevent EFAD.
Aminosyn II 8.5% with electrolytes
DOSAGE AND ADMINISTRATION:
ADULTS
Second to last paragraph: Aminosyn II 8,5% solution, when mixed with an appropriate volume of concentrated dextrose, offers a higher concentration of calories and hydrogen per unit volume. This solution is indicated for patients requiring larger amounts of nitrogen than could otherwise be provided or where total fluid load must be kept to a minimum, for example, patients with renal failure.
Aminosyn PF 10% 1000 mL/Pharmacy Bulk Package flexible plastic container-closure system.
DESCRIPTION:
First paragraph is revised as follows:
Aminosyn P/F 10% Sulfite-free (an amino acid injection – pediatric formula) is a sterile, nonpyrogenic formulation for intravenous infusion. Aminosyn PF 10% is oxygen sensitive. The Pharmacy Bulk Package is a sterile dosage form which contains multiple single doses for use only in a pharmacy bulk admixture program.
The Pharmacy Bulk package is designed for use with manual, gravity flow operations and automated compounding devices for preparing sterile parenteral nutrient admixtures; it contains no bacteriostat. Multiple single doses may be dispensed during continual aliquoting operations. Withdrawal of container contents should be promptly completed within 4 hours after initial closure puncture.
DOSAGE AND ADMINISTRATION:
Recommended Directions for Use of the Pharmacy Bulk package
USE Aseptic technique
1. During use, container must be stored, and all manipulations performed, in an appropriate laminar flow hood.
2. Aseptically remove aluminum overseal Remove cover from outlet port at bottom of container.
3. Insert piercing pin of sterile transfer set and suspend unit in laminar flow hood.* Insertion of a piercing pin into the outlet port should be performed only once in a Pharmacy Bulk Package solution. Once the outlet site has been entered, the withdrawal of container contents should be completed promptly in one continuous operation. Should this not be possible, a maximum time of 4 hours from transfer set pin or implement insertion is permitted to complete fluid transfer operations; i.e., discard container no later than 4 hours after initial closure puncture.
4. Sequentially dispense aliquots of Aminosyn-PF 10% into I.V. containers using appropriate transfer set. During fluid transfer operations, the Pharmacy Bulk Package should be maintained under the storage conditions recommended in the labeling.
Additives may be incompatible with fluid withdrawn from this container. Consult with pharmacist, if available. When compounding admixtures, use aseptic technique. Mix thoroughly. Do not store solutions containing additives. Because of the potential for life-threatening events, caution should be taken to ensure that precipitates have not formed in any parenteral nutrient mixture.
* Insertion
of a piercing pin or needle into the target area of the rubber stopper should
be performed only once in a Pharmacy Bulk Package solution without an antimicrobial
preservative. The time frame permitted for container withdrawals should be as
brief as possible, usually no longer than needed to systematically complete
aliquoting opearations without interruption.
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AndroGel (testosterone) 1% Gel
[October 1, 2002: Unimed Pharmaceuticals ]
DOSAGE AND ADMINISTRATION
Upon opening the packet(s), the entire contents should be squeezed into the palm of the hand and immediately applied to the application sites. Alternately, patients may squeeze a portion of the gel from the packet into the palm of the hand and apply to application sites. Repeat until entire contents have been applied.
Patient Information and Instructions for Using AndroGel 1%
(testosterone gel) C-III
What is AndroGel?
AndroGel is a clear, colorless gel medicine that delivers testosterone into
your body through your skin. Once AndroGel is absorbed through your skin, it
enters your bloodstream and helps your body reach normal testosterone levels.
The type of testosterone delivered into your body by AndroGel is the same as
the testosterone produced in your testicles
AndroGel has been shown to improve quality and duration
of erections, increase libido,
decrease fatigue, increase lean body mass, decrease fat mass, increase bone
mineral density, and
improve mood.
AndroGel has been shown to: improve quality and duration
of erections, increase libido, decrease
fatigue, increase lean body mass, decrease fat mass, increase bone mineral density,
and improve mood.
Who should not take AndroGel?
You should not use AndroGel if you have any of the following conditions:
Tell your doctor about other medicines you are taking. AndroGel may affect how these medicines work, and you may need to have your doses adjusted.
How should I use AndroGel?
1.Apply AndroGel AndroGel at the same time
each day
(preferably every morning). You should
apply the contents of one (1) packet of gel every morning. If you take a bath
or shower in the morning, use AndroGel after your bath or shower. Your
doctor will tell you how
much AndroGel to use more
than one packet at a time each
day.
3.Open the packet. Open one AndroGel aluminum
foil packet by folding the top edge at
the perforation and tearing completely across the packet along the perforation.
and tearing open
the packet.
4.Remove the contents from the packet.
Squeeze the entire
contents into the palm of your hand.
Squeeze from the bottom of the packet toward the top. If
you like, you can squeeze out half (1/2) of the contents of the packet at
a time and then squeeze out the second half after you have applied the first
half, following the directions below.
If you like, you may squeeze
a portion of the gel from the packet into the palm of your hand and apply
to application site(s). Repeat until
the entire contents of the packet have been applied.
"Men should apply gel to starred (upper arm/shoulders) or shaded (abdomen) areas".
For picture of male figure, contact the company for a copy of the new labeling/package insert.
5.Apply AndroGel only to your abdomen (stomach area), shoulders, or upper arms. In this way your body will absorb the right amount of testosterone. Never apply AndroGel to your genitals (penis and scrotum) or to damaged skin. Apply AndroGel only to healthy, normal skin. Avoid skin with open sores, wounds, or irritation. Use a circular motion to rub the gel for several seconds. Apply AndroGel only to healthy, normal skin on your abdomen (stomach area), shoulders, or upper arms. In this way your body will absorb the right amount of testosterone. Never apply AndroGel to your genitals (penis or scrotum) or to skin with open sores, wounds or irritation.
What are the possible side effects of AndroGel?
Tell your doctor if you develop any of the following side effects:
[Fourth bullet]
· difficulty urinating
Tell your doctor about other medicines you are taking. AndroGel may affect how these medicines work, and you may need to have your doses adjusted.
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ARIMIDEX (anastrozole) Tablets
[October 7, 2002: AstraZeneca]
[Other labeling changes not in 2002 PDR: http://www.fda.gov/medwatch/SAFETY/2002/sep02.htm#arimid]
ADVERSE REACTIONS
Second Line Therapy:
Arimidex may also be associated with rash including very rare cases of mucocutaneous disorders such as erythema multiforme and Stevens-Johnson syndrome.
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BUMEX (bumetanide) Tablets & Injection
[October 29, 2002: Hoffmann-La Roche]
CLINICAL PHARMACOLOGY
Pediatric Pharmacology
First paragraph, last sentence of the "Mean volume of distribution in neonates has been reported to range from 0.26 L/kg to 0.39 L/kg." was moved to the last sentence of the second paragraph.
First paragraph, last sentence was replaced with -
Elimination half-life decreased considerably during the first month of life, from a mean of approximately 6 hours at birth to approximately 2.4 hours at 1 month of age.
Last paragraph revised:
In 56 infants aged 4 days to 6 months, Bumex doses ranging from 0.005 mg/kg to 0.1 mg/kg were studied for pharmacodynamic effect. Peak bumetanide excretion rates increased linearly with increasing doses of drug. Maximal diuretic effect was observed at a bumetanide excretion rate of about 7 mcg/kg/hr, corresponding to doses of 0.035 to
0.040 mg/kg. Higher doses produced a higher bumetanide excretion rate but no increase in diuretic effect. Urine flow rate peaked during the first hour after drug administration in 80% of patients and by 3 hours in all patients.
CLINICAL PHARMACOLOGY
Geriatric Pharmacology
In a group of ten geriatric subjects between the ages of 65 and 73 years, total bumetanide clearance was significantly lower (1.8 ± 0.3 mL/min·kg) compared with younger subjects (2.9 ± 0.2 mL/min·kg) after a single oral bumetanide 0.5 mg dose. Maximum plasma concentrations were higher in geriatric subjects (16.9 ± 1.8 ng/mL) compared with younger subjects (10.3 ± 1.5 ng/mL). Urine flow rate and total excretion of sodium and potassium were increased less in the geriatric subjects compared with younger subjects, although potassium excretion and fractional sodium excretion were similar between the two age groups. Nonrenal clearance, bioavailability, and volume of distribution were not significantly different between the two groups.
PRECAUTIONS
Geriatric Use
Clinical studies of Bumex did not include sufficient numbers of subjects aged 65 and over to determine whether they responded differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.
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COMBIVIR (lamivudine/zidovudine) Tablets
[October 8, 2002: GlaxoSmithKline]
[Other labeling changes not in 2002 PDR: http://www.fda.gov/medwatch/SAFETY/2002/aug02.htm#combiv]
Labeling provides for the addition of fat redistribution information. Contact the company for a copy of the new labeling/package insert.
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COSMEGEN (Dactinomycin) Injection
[October 28, 2002:Merck]
PRECAUTIONS
Geriatric Use
Clinical studies of COSMEGEN did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. However, a published meta-analysis of all studies performed by the Eastern Cooperative Oncology Group (ECOG) over a 13-year period suggests that administration of COSMEGEN to elderly patients may be associated with an increased risk of myelosuppression compared to younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
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DARAPRIN (pyrimethamine) Tablets
[October 10, 2002: GlaxoSmithKline]
PRECAUTIONS:
Geriatric Use: Clinical studies of DARAPRIM did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
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EFFEXOR XR (venlafaxine HCl) Extended Release Capsules
[October 22, 2002: Wyeth-Ayerst]
DOSAGE AND ADMINISTRATION
Effexor XR should be administered in a single dose with food either in the morning or in the evening at approximately the same time each day. Each capsule should be swallowed whole with fluid and not divided, crushed, chewed, or placed in water, or it may be administered by carefully opening the capsule and sprinkling the entire contents on a spoonful of applesauce. This drug/food mixture should be swallowed immediately without chewing and followed with a glass of water to ensure complete swallowing of the pellets.
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EPIVIR (lamivudine) Tablets & Oral Solution
[October 8, 2002: GlaxoSmithKline]
[Other labeling changes not in 2002 PDR: http://www.fda.gov/medwatch/SAFETY/2002/mar02.htm#epivir,
http://www.fda.gov/medwatch/SAFETY/2002/jun02.htm#epivir]
PRECAUTIONS
Pregnancy:
In 2 clinical studies conducted in South Africa, pharmacokinetic measurements were performed on samples from pregnant women who received lamivudine beginning at week 38 of gestation (10 women who received 150 mg twice daily in combination with zidovudine and 10 who received lamivudine 300 mg twice daily without other antiretrovirals) or beginning at week 36 of gestation (16 women who received lamivudine 150 mg twice daily in combination with zidovudine). These studies were not designed or powered to provide efficacy information. Lamivudine pharmacokinetics in the pregnant women were similar to those obtained following birth and in non-pregnant adults. Lamivudine concentrations were generally similar in maternal, neonatal, and cord serum samples. In a subset of subjects from whom amniotic fluid specimens were obtained following natural rupture of membranes, amniotic fluid concentrations of lamivudine ranged from 1.2 to 2.5 mcg/mL (150 mg twice daily) and 2.1 to 5.2 mcg/mL (300 mg twice daily) and were typically greater than 2 times the maternal serum levels. See the ADVERSE REACTIONS section for the limited late-pregnancy safety information available from these studies. Lamivudine should be used during pregnancy only if the potential benefits outweigh the risks.
Pediatric Use: HIV: Limited, uncontrolled pharmacokinetic and safety data are available from.administration of lamivudine (and zidovudine) to 36 infants up to 1 week of age in 2 studies in South Africa. In these studies, lamivudine clearance was substantially reduced in 1-week-old neonates relative to pediatric patients (>3 months of age) studied previously. There is insufficient information to establish the time course of changes in clearance between the immediate neonatal period and the age ranges >3 months old. See the ADVERSE REACTIONS section for the limited safety information available from these studies.
ADVERSE REACTIONS
Pediatric Patients:
Limited short-term safety information is available from 2 small, uncontrolled studies in South Africa in neonates receiving lamivudine with or without zidovudine for the first week of life following maternal treatment starting at week 38 or 36 of gestation (see PRECAUTIONS: Pediatric Use). Adverse events reported in these neonates included increased liver function tests, anemia, diarrhea, electrolyte disturbances, hypoglycemia, jaundice and hepatomegaly, rash, respiratory infections, sepsis, and syphilis; 3 neonates died (1 from gastroenteritis with acidosis and convulsions, 1 from traumatic injury, and 1 from unknown causes). Two other nonfatal gastroenteritis or diarrhea cases were reported, including 1 with convulsions; 1 infant had transient renal insufficiency associated with dehydration.
The absence of control groups further limits assessments of causality, but it should be assumed that perinatally exposed infants may be at risk for adverse events comparable to those reported in pediatric and adult HIV-infected patients treated with lamivudine-containing combination regimens. Long-term effects of in utero and infant lamivudine exposure are not known.
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ETHRANE (enflurane) Liquid for Inhalation
[October 8, 2002:Baxter Healthcare]
ADVERSE REACTIONS:
3. Hypotension, respiratory depression, and hypoxia have been reported.
6. Unexplained
Mild, moderate and severe liver injury, including
hepatic failure, may rarely follow anesthesia
with enflurane.
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IDAMYCIN (idarubicin HCl) Injection
[October 11, 2002: Pharmacia & Upjohn]
PRECAUTIONS
Geriatric Use
Patients over 60 years of age who were undergoing induction therapy experienced congestive heart failure, serious arrythmias, chest pain, myocardial infarction, and asymptomatic declines in LVEF more frequently than younger patients (see ADVERSE REACTIONS).
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LARIAM (mefloquine HCl) Tablets
[October3, 2002: Hoffman-LaRoche]
CONTRAINDICATIONS
Use of Lariam is contraindicated in patients with
a known hypersensitivity to mefloquine or related compounds (eg, quinine and
quinidine). Lariam should not be prescribed for prophylaxis in patients with
active depression, a recent
history of depression, generalized anxiety disorder, psychosis, or schizophrenia
or other major psychiatric disorders, or
with a history of psychosis
or convulsions.
WARNINGS
Mefloquine may cause psychiatric symptoms in a number of patients, ranging from anxiety, paranoia, and depression to hallucinations and psychotic behavior. On occasions, these symptoms have been reported to continue long after mefloquine has been stopped. Rare cases of suicidal ideation and suicide have been reported though no relationship to drug administration has been confirmed. To minimize the chances of these adverse events, mefloquine should not be taken for prophylaxis in patients with active depression or with a recent history of depression, generalized anxiety disorder, psychosis, or schizophrenia or other major psychiatric disorders. Lariam should be used with caution in patients with a previous history of depression.
During prophylactic use, if psychiatric symptoms such as acute anxiety, depression, restlessness or confusion occur, these may be considered prodromal to a more serious event. In these cases, the drug must be discontinued and an alternative medication should be substituted.
PRECAUTIONS
Second paragraph - the following two sentences were deleted:
During prophylactic use, if signs of acute anxiety, depression, restlessness or confusion occur, these may be considered prodromal to a more serious event. In these cases, the drug must be discontinued.
Information for Patients
Second bullet -
that if the patient experiences any symptom that may affect the patients’s ability to take this drug as prescribed, the physician should be contacted and alternative antimalarial patients experience psychiatric symptoms such as acute anxiety, depression, restlessness or confusion, these may be considered prodromal to a more serious event. In these cases, the drug must be discontinued and an alternative medication should be considered substituted;
ADVERSE REACTIONS
Postmarketing
Postmarketing surveillance indicates that the same kind of adverse experiences are reported during prophylaxis, as well as acute treatment.
The most common adverse reactions to Lariam prophylaxis, namely nausea, vomiting, and dizziness, are generally mild and may decrease with prolonged use, in spite of increasing plasma drug levels. In a large study of tourists receiving various prophylactic antimalarials, the rate of subjects reporting adverse events on Lariam was similar to that of tourists on chloroquine.
The most frequently reported adverse events are nausea, vomiting, loose stools or diarrhea, abdominal pain, dizziness or vertigo, loss of balance, and neuropsychiatric events such as headache, somnolence, and sleep disorders (insomnia, abnormal dreams). loose stools or diarrhea, and abdominal pain. These are usually mild and may decrease despite continued use.
Less frequently reported adverse events:
Central and peripheral nervous system: Convulsions, depression, hallucinations, psychotic or paranoid reactions, anxiety, agitation, aggression, confusion, forgetfulness, hearing impairment, restlessness, Occasionally, more severe neuropsychiatric disorders have been reported such as: sensory and motor neuropathies (including paresthesia, tinnitus and vestibular disorders, visual disturbances. Suicidal tremor and ataxia), convulsions, agitation or restlessness, anxiety, depression, mood changes, panic attacks, forgetfulness, confusion, hallucinations, aggression, psychotic or paranoid reactions ideation has also rarely been reported, but and encephalopathy. Rare cases of suicidal ideation and suicide have been reported though no relationship to drug administration has been established confirmed.
Other infrequent adverse events include:
Cardiovascular system Disorders: circulatory disturbances (hypotension, hypertension, flushing, syncope), chest pain, tachycardia or palpitation, bradycardia, irregular pulse, extrasystoles, A-V block, and other transient cardiac conduction alterations.
Skin Disorders: rash, exanthema, erythema, urticaria, pruritus, edema, hair loss, sweating, erythema multiforme, and Stevens-Johnson syndrome.
Musculoskeletal system Disorders: muscle weakness, muscle cramps, myalgia, and arthralgia.
General Other Symptoms: visual disturbances, vestibular disorders including tinnitus and hearing impairment, dyspnea, asthenia, malaise, fatigue, fever, sweating, chills, dyspepsia and loss of appetite.
Isolated cases of erythema multiforme, Stevens-Johnson syndrome, AV-block, and encephalopathy, have been reported.
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LEVAQUIN (levofloxacin) Tablets & Injection
[October 30, 2002: Johnson & Johnson]
Labeling provides for the use of Levaquin Tablets and Injection for the treatment of nosocomial pneumonia. Contact the company for a copy of the new labeling/package insert.
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LIPITOR (atorvastatin calcium) Tablets
[October18, 2002: Pfizer]
[Other labeling changes not in 2002 PDR: http://www.fda.gov/medwatch/SAFETY/2002/apr02.htm#lipito]
Labeling provides for the addition of an indication for the treatment of heterozygous familial hypercholesterolemia in adolescent boys and postmenarchal girls, ages 10 to 17 years, with a recommended dosing range of 10 to 20 mg once daily. Contact the company for a copy of the new labeling/package insert.
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MYKROX (metolazone) Tablets
&
ZAROXOLYN (metolazone) Tablets
[October 29, 2002: Celltech]
PRECAUTIONS
Geriatric Use
Clinical studies of (Mykrox, Zaroxolyn) did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal or cardiac function, and of concomitant disease or other drug therapy.
This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.
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PAXIL (paroxetine HCL) Tablets
[October 2, 2002: GlaxoSmithKline]
Labeling provides for the longer-term use of Paxil (paroxetine hydrochloride) Tablets for the treatment of generalized anxiety disorder (GAD).
Contact the company for a copy of the new labeling/package insert.
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[October 21, 2002: Novo Nordisk]
[Other labeling changes not in 2002 PDR: http://www.fda.gov/medwatch/SAFETY/2002/jan02.htm#prandi]
Labeling provides for the use of Prandin (repaglinide) Tablets in combination with a thiazolidinedione to lower blood glucose in patients with type 2 diabetes whose hyperglycemia cannot be controlled by diet and exercise plus monotherapy with any of the following agents: metformin, sulfonylureas, repaglinide, or thiazolidinediones. Contact the company for a copy of the new labeling/package insert.
CLINICAL PHARMACOLOGY
Drug-Drug Interactions:
Clarithromycin: Co-administration of 250 mg clarithromycin and a single dose of 0.25 mg PRANDIN (after 4 days of twice daily clarithromycin 250 mg) resulted in a 40% and 67% increase in repaglinide AUC and Cmax, respectively. The increase in AUC was from 5.3 ng/mL*hr. to 7.5 ng/mL*hr and the increase in Cmax was from 4.4 ng/mL to 7.3 ng/mL.
PRECAUTIONS
Drug Interactions
In vivo data from a study that evaluated the co-administration of a cytochrome P450 enzyme inhibitor, clarithromycin, with PRANDIN resulted in a clinically significant increase in repaglinide plasma levels. This increase in repaglinide plasma levels may necessitate a PRANDIN dose adjustment. See CLINICAL PHARMACOLOGY section, Drug-Drug Interactions.
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PRAVACHOL (pravastatin sodium) Tablets
[October 29, 2002: Bristol-Myers Squibb]
[Other labeling changes not in 2002 PDR: http://www.fda.gov/medwatch/SAFETY/2002/jul02.htm#pravac,
http://www.fda.gov/medwatch/SAFETY/2002/jul02.htm#pravac]
Labeling provides for the addition of an indication for the treatment of heterozygous familial hypercholesterolemia in children, ages 8 to 13 years, with a recommended dose of 20 mg once daily and in adolescents, ages 14 to 18, with a recommended dose of 40 mg once daily. Contact the company for a copy of the new labeling/package insert.
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[October 29, 2002: Bayer]
CLINICAL PHARMACOLOGY
Drug-Drug Interactions: Studies in healthy volunteers have shown that Precose has no effect on either the pharmacokinetics or pharmacodynamics of nifedipine, propranolol, or ranitidine. Precose did not interfere with the absorption or disposition of the sulfonylurea glyburide in diabetic patients. In individual cases, Precose may affect digoxin bioavailability and may require dosage adjustment of digoxin. Drug interaction studies show that Precose decreases mean bioavailability (AUC) of digoxin by 16% (90% confidence interval: 8-23%), decreases mean Cmax of digoxin by 26% (90% confidence interval: 16-34%), and decreases mean trough concentration of digoxin by 9% (90% confidence limit: 19% decrease to 2% increase). (See PRECAUTIONS, Drug Interactions).
PRECAUTIONS
Drug Interactions
PRECOSE has been shown to change the bioavailability of digoxin when they are co-administered, which may require digoxin dose adjustment." (See CLINICAL PHARMACOLOGY, Drug-Drug Interactions).
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PROTONIX (pantoprazole sodium) Delayed-Release Tablets & Injection
[October 28, 2002: Wyeth]
[Other labeling changes not in 2002 PDR: http://www.fda.gov/medwatch/SAFETY/2002/apr02.htm#proton]
PRECAUTIONS:
Laboratory Tests
There have been reports of false-positive urine screening tests for tetrahydrocannabinol (THC) in patients receiving pantoprazole.
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Renografin-60 ( Diatrizoate Meglumine and Diatrizoate Sodium) Injection
[October 23, 2002: Bracco Diagnostics]
WARNINGS
Severe Adverse Events-Inadvertent Intrathecal Administration
The possibility exists for inadvertent administration into the intrathecal space during epidural administrations. Therefore, epidural administrative procedures, such as pain management catheter placement, should not be performed with use of this product.
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TEQUIN (gatifloxacin HCl) Tablets & Injection
[October 17, 2002: Bristol-Myers Squibb]
CLINICAL PHARMACOLOGY
Electrocardiogram
In volunteer studies asessing oral and IV doses ranging from 200 to 800 mg, 55 subjects had 76 paired valid ECGs. There were not subjects with abnormal QTc intervals (>450 msec); the mean ± SD change in QTc interval was 2.9 ± 16.5 msec.
In pre-marketing studies of volunteer subjects with pre- and post-dose ECGs obtained in 55 male volunteers receiving oral or IV TEQUIN doses of 200 to 800 mg, the mean change in the post-dose QTc interval was <10 msec and there were no subjects with prolonged post-dose QTc intervals of >450 msec. In a post-marketing study of 34 healthy male and female volunteers receiving single oral doses of TEQUIN 400, 800 and 1200 mg and placebo, an association between increases in post-dose QTc interval changes from baseline and increases in gatifloxacin plasma concentrations were observed. At the therapeutic dose of 400 mg, the mean change in post-dose QTc interval from baseline was <10 msec. There were no subjects with prolonged post-dose QTc intervals of >450 msec for males and >470 msec for females.
In a post-marketing clinical trial of 262 patients with respiratory tract infections receiving repeated 400 mg oral doses of TEQUIN who were studied with pre- and post-dose ECGs, the mean change in the post-dose QTc interval was <10 msec following the first 400 mg dose. In another post-marketing study of patients with an acute coronary syndrome occurring within 4 weeks prior to TEQUIN administration, pre- and post-dose ECGs were obtained in patients who were administered TEQUIN 400 mg orally after single (N=372) and repeated (steady state; N=36) dosing. The mean changes in the post-dose QTc interval in these patients were <10 msec after both single and repeated dosing.
There is limited information available on the potential for a pharmacodynamic interaction in humans between gatifloxacin and drugs that prolong the QTc interval of an electrocardiogram. Therefore, gatifloxacin should not be used with Class IA and Class III antiarrhythmics cisapride, erythromycin, antipsychotics, and tricyclic antidepressants (see WARNINGS and PRECAUTIONS: Information for Patients).
WARNINGS
Prolongation of the QTc Interval
GATIFLOXACIN MAY
HAVE HAS THE POTENTIAL
TO PROLONG THE QTc INTERVAL OF THE ELECTROCARDIOGRAM IN SOME PATIENTS.
DUE TO THE LACK OF CLINICAL EXPERIENCE, GATIFLOXACIN SHOULD BE AVOIDED
IN PATIENTS WITH KNOWN PROLONGATION OF THE QTc INTERVAL, PATIENTS WITH UNCORRECTED
HYPOKALEMIA, AND PATIENTS RECEIVING CLASS IA (E.G., QUINIDINE, PROCAINAMIDE)
OR CLASS III (E.G., AMIODARONE, SOTALOL) ANTIARRHYTHMIC AGENTS.
GATIFLOXACIN SHOULD BE AVOIDED IN THESE PATIENT POPULATIONS.
Pharmacokinetic and
pharmacodynamic studies between gatifloxacin
and drugs that prolong the QTc interval such as cisapride, erythromycin,
antipsychotics, and tricyclic antidepressants have
not been performed. Gatifloxacin should be used with caution when given concurrently
with these drugs, as well as in patients with ongoing proarrhythmic conditions,
such as clinically significant bradycardia or acute myocardial ischemia. In
premarketing clinical trials, no cardiovascular morbidity or mortality attributable
to QTc prolongation occurred with gatifloxacin treatment in over 4000 patients,
including 118 patients concurrently receiving drugs known to prolong the QTc
interval and 139 patients with
uncorrected hypokalemia (ECG monitoring was not performed).
The likelihood magnitude of QTc prolongation may increase increases with increasing concentrations of the drug; therefore, the recommended dose and the recommended intravenous infusion rate should not be exceeded (see DOSAGE AND ADMINISTRATION for dosing recommendations for patients with or without renal impairment). QTc prolongation may lead to an increased risk for ventricular arrhythmias including torsades de pointes (see CLINICAL PHARMACOLOGY: Electrocardiogram).
No cardiovascular morbidity or mortality attributable to QTc prolongation has occurred in over 44,000 patients treated with gatifloxacin in clinical trials; these include 118 patients concurrently receiving drugs known to prolong the QTc interval and 139 patients known to have uncorrected hypokalemia (ECG monitoring was not performed). During postmarketing surveillance, rare cases of torsades de pointes have been reported in patients taking gatifloxacin. These cases have occurred primarily in elderly patients with underlying medical problems for which they were receiving concomitant medications known to prolong the QTc interval; the contribution, if any, of gatifloxacin to the development of torsades de pointes in these patients is unknown.
CLINICAL PHARMACOLOGY
Glucose Homeostasis
Disturbances in Blood Glucose
Disturbances of blood glucose, including symptomatic hyper- and hypoglycemia, have been reported with TEQUIN (as with other quinolones), usually in diabetic patients. Therefore, careful monitoring of blood glucose is recommended when TEQUIN is administered to patients with diabetes (see WARNINGS, PRECAUTIONS: General, Information for Patients and Drug Interactions, and ANIMAL PHARMACOLOGY).
In a post-marketing study conducted in non-infected patients (N=70) with Type 2 diabetes mellitus controlled primarily with either the combination of glyburide and metformin or metformin alone, daily administration of gatifloxacin 400 mg orally for 14 days was associated with initial hypoglycemia followed by hyperglycemia. Upon initiation of gatifloxacin dosing (i.e., first two days of treatment), there were increases in serum insulin concentrations and resulting decreases in serum glucose, as compared to baseline glucose values, despite ingestion of dietary restricted meals. In some patients, the reductions in glucose produced signs and symptoms of hypoglycemia (asthenia, sweating, dizziness) and necessitated administration of additional food. With continued gatifloxacin dosing (i.e., from the third day of treatment and throughout the dosing period), fasting serum glucose concentrations were increased compared to baseline. The serum glucose concentrations returned to baseline in most of these uninfected patients by 28 days after the cessation of gatifloxacin treatment. Single doses of insulin were administered to 3 patients in this study to correct the hyperglycemia during continued gatifloxacin administration.
In two pre-marketing studies,
Nno
clinically significant changes in glucose tolerance (via measurement
of oral glucose challenge) and glucose homeostasis (via measurement of
fasting serum glucose, serum insulin and c-peptide) were observed following
single or multiple intravenous infusion doses of 200 to 800 mg TEQUIN in healthy
volunteers (N=30),
or 400-mg oral doses of TEQUIN for 10 days in patients (N=16)
with Type 2 (non-insulin-dependent)
diabetes mellitus) controlled
on diet and exercise. Compared
to placebo, Ttransient
modest increases in serum insulin of
approximately 20-40% and decreases in glucose
concentrations of approximately
30% were noted with the first dose of intravenous
or oral gatifloxacin. Following
multiple oral doses of TEQUIN in patients with Type 2 non-insulin-dependent
diabetes mellitus controlled with glyburide, decreases in serum insulin concentrations
were noted following oral glucose challenge; however, these decreases were not
accompanied by changes in serum glucose levels. (See PRECAUTIONS: General.)
In another pre-marketing study, following administration of single oral 400-mg doses of TEQUIN for 10 days in patients (N=16) with Type 2 diabetes mellitus controlled with glyburide, decreases in serum insulin concentrations of approximately 30-40%, as compared to placebo, were noted following oral glucose challenge; however, these decreases were not accompanied by statistically significant changes in serum glucose levels. In this study, modest increases in fasting glucose (average increases of 40 mg/dL) were also noted by day 4 of continued gatifloxacin administration, although these changes did not reach statistical significance.
Drug-Drug Interactions
GLYBURIDE
Concomitant administration of TEQUIN (once daily oral doses of 400 mg for 10 days) and glyburide (steady-state once daily regimen) in patients with type 2 diabetes mellitus had no significant effects on the disposition of either drug. These results are consistent with the lack of effect of TEQUIN in in vitro studies with the human CYP3A4 isoenzyme. However, pharmacodynamic changes have been seen with concomitant glyburide use (see PRECAUTIONS: General and Drug Interactions).
Glyburide: Concomitant administraton Pharmacodynamic changes in glucose homeostasis were seen with concomitant administration of TEQUIN (once daily oral doses of 400 mg for 10 days) and glyburide (steady-state once daily regimen) in patients with type 2 diabetes mellitus. This was not associated with had no significant effects on the pharmacokinetic disposition of either drug , nor were the fasting glucose levels significantly changed. These latter results are consistent with the lack of effect of TEQUIN in in vitro studies with the human CYP3A4 isoenzyme. (see PRECAUTIONS: General and Drug Interactions CLINICAL PHARMACOLOGY: Glucose Homeostasis and WARNINGS).
Disturbances in Blood Glucose
Disturbances of blood glucose, including symptomatic hyper- and hypoglycemia, have been reported with TEQUIN, usually in diabetic patients. Therefore, careful monitoring of blood glucose is recommended when TEQUIN is administered to patients with diabetes (See CLINICAL PHARMACOLOGY, PRECAUTIONS: Information for Patients and Drug Interactions, and ANIMAL PHARMACOLOGY).
Studies conducted in patients with Type 2 diabetes mellitus controlled on oral hypoglycemic agents have demonstrated that TEQUIN is associated with disturbances in glucose homeostasis including an increase in serum insulin and decrease in serum glucose usually following administration of initial doses (i.e., first two days of treatment), and sometimes associated with symptomatic hypoglycemia. Increases in fasting serum glucose were also observed, usually after the third day of TEQUIN administration, continuing throughout the duration of treatment, and returning to baseline by 28 days after the cessation of gatifloxacin treatment in most patients.
During the postmarketing period, there have been reports of serious disturbances of glucose homeostasis in patients being treated with TEQUIN. Hypoglycemic episodes, in some cases severe, have been reported in patients with diabetes mellitus treated with either sulfonylurea or non-sulfonylurea oral hypoglycemic medications. These events frequently occurred on the first day of therapy and usually within 3 days following the initiation of TEQUIN. Hyperglycemic episodes, in some cases severe and associated with hyperosmolar non-ketotic hyperglycemic coma, were reported in diabetic patients, mostly between 4 and 10 days following the initiation of TEQUIN therapy. Some of the hyperglycemic and hypoglycemic events were life-threatening and many required hospitalization, although these events were reversible when appropriately managed.
Many of these patients had other underlying medical problems and were receiving concomitant medications that may have contributed to the glucose abnormality. Episodes of hyperglycemia, including hyperosmolar non-ketotic hyperglycemic coma, also occurred in patients not previously diagnosed with diabetes mellitus. Elderly patients who may have unrecognized diabetes, age-related decrease in renal function, underlying medical problems and/or are taking concomitant medications associated with hyperglycemia may be at particular risk of serious hyperglycemia.
The dose of TEQUIN should be adjusted based on underlying renal function (see DOSING AND ADMINISTRATION). When TEQUIN is used in diabetic patients, blood glucose should be closely monitored. Signs and symptom of hypoglycemia should be monitored, especially during the first three days of therapy, and signs and symptoms of hyperglycemia should be monitored in diabetics and patients who may be at risk for hyperglycemia, especially with continued treatment with TEQUIN beyond three days. If signs and symptoms of either hypoglycemia or hyperglycemia occur in any patient being treated with TEQUIN, appropriate therapy must be initiated immediately and TEQUIN should be discontinued.
PRECAUTIONS
Information for Patients
● that disturbances of blood glucose, including symptomatic hyper- and hypoglycemia, have been reported with Tequin (as with other quinolones), usually in diabetic patients or in patients at risk for hyperglycemia. If a hypoglycemic reaction or symptoms of hyperglycemia occur, patients should initiate appropriate therapy immediately, discontinue TEQUIN, and contact a their physician (see PRECAUTIONS: General and Drug Interactions CLINICAL PHARMACOLOGY and WARNINGS).
Drug Interactions
Antidiabetic agents: No significant
pharmacokinetic interactions have been observed when glyburide was administered
concomitantly with TEQUIN. However, disturbances of blood glucose, including
symptomatic hyper- and hypoglycemia, have been reported in patients treated
concomitantly with TEQUIN (as with other quinolones) and oral hypoglycemic agents
with or without insulin. Therefore, careful monitoring of blood glucose is recommended
when TEQUIN is administered to diabetic patients receiving treatment with oral
hypoglycemic agents with or without insulin (see CLINICAL PHARMACOLOGY and PRECAUTIONS:
General and Information for Patients).
Antidiabetic agents: Pharmacodynamic changes in glucose homeostasis have been seen with concomitant glyburide use. However, no significant pharmacokinetic interactions have been observed when glyburide was administered concomitantly with TEQUIN. (see CLINICAL PHARMACOLOGY: Glucose Homeostasis and WARNINGS).
ANIMAL PHARMACOLOGY
In three animal species (rats, beagle dogs, and cynomolgus monkeys) given oral gatifloxacin doses approximately 1.0- to 19-times the approved human dose (based on body surface area) from one to six months, electron microscopy showed vesiculation of rough endoplasmic reticulum and decreased secretory granules in pancreatic ß-cells of all three species. These ultrastructural changes correlated with vacuolation of pancreatic b -cells seen by light microscopy in dogs given a dose level for one or six months that was approximately equivalent to the human dose (based upon body surface area and plasma AUC). Following a 4-week recovery period without gatifloxacin, partial recovery from these pancreatic changes was seen in the rat and complete recovery was evident in beagle dogs and cynomologus monkeys (see WARNINGS and CLINICAL PHARMACOLOGY).
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[October 1, 2002: Forest Laboratories]
PRECAUTIONS & HOW SUPPLIED
Tablets should be stored at cold temperature, between 36° and 46°F (2° and 8°C) in a tight, light-resistant container.
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TRIZIVIR (abacavir sulfate, lamivudine, and zidovudine) Tablets
[October 8, 2002: GlaxoSmithKline]
[Other labeling changes not in 2002 PDR: http://www.fda.gov/medwatch/SAFETY/2002/jun02.htm#triziv,
http://www.fda.gov/medwatch/SAFETY/2002/aug02.htm#triziv ]
ADVERSE REACTIONS
Fourth paragraph -
In clinical studies, approximately 5% of adult and pediatric patients receiving abacavir developed a hypersensitivity reaction. This reaction is characterized by the appearance of symptoms indicating multi-organ/body system involvement. Symptoms usually appear within the first 6 weeks of treatment with abacavir, although these reactions may occur at any time during therapy. Frequently observed signs and symptoms include fever, skin rash, fatigue, and gastrointestinal symptoms such as nausea, vomiting, diarrhea, or abdominal pain. Other signs and symptoms include malaise, lethargy, myalgia, myolysis, arthralgia, edema, cough, abnormal chest x-ray findings (predominantly infiltrates, which can be localized), dyspnea, headache, and paresthesia. Some patients who experienced a hypersensitivity reaction were initially thought to have acute onset or worsening respiratory disease. The diagnosis of hypersensitivity reaction should be carefully considered for patients presenting with symptoms of acute onset respiratory diseases, even if alternative respiratory diagnoses (pneumonia, bronchitis, flu-like illness) are possible.
Fifth and sixth paragraphs -
Physical findings include lymphadenopathy, mucous membrane lesions (conjunctivitis and mouth ulcerations), and rash. The rash usually appears maculopapular or urticarial but may be variable in appearance. There have been reports of erythema multiforme. Hypersensitivity reactions have occurred without rash.
Laboratory abnormalities include elevated liver function tests, increased creatine phosphokinase or creatinine, and lymphopenia. Anaphylaxis, liver failure, renal failure, hypotension, adult respiratory distress syndrome, respiratory failure, and death have occurred in association with hypersensitivity reactions. Symptoms worsen with continued therapy but often resolve upon discontinuation of abacavir.
Observed During Clinical Practice:
Abacavir: Suspected Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported in patients receiving abacavir primarily in combination with medications known to be associated with SJS and TEN, respectively. Because of the overlap of clinical signs and symptoms between hypersensitivity to abacavir and SJS and TEN, and the possibility of multiple drug sensitivities in some patients, abacavir should be discontinued and not restarted in such cases.
There have also been reports of erythema multiforme with abacavir use.
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VASERETIC (enalapril maleate/hydrochlorothiazide)
Tablets
&
VASOTEC (enalaprilat) I.V.
[October 30, 2002: Merck]
PRECAUTIONS:
Geriatric Use
Clinical studies of (VASERETIC and VASOTEC I.V.) did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection. Evaluation of the hypertensive patient should always include assessment of renal function. (See DOSAGE AND ADMINISTRATION.)
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[October 1, 2002: Bristol-Myers Squibb]
PRECAUTIONS
Pediatric Use: Adverse events were evaluated in 7 studies involving 303 patients (age-range 0.5 months to 20 years) who received Vumon as a single agent (see ADVERSE REACTIONS). No association between any particular age group and adverse effects was reported in any of these investigations.
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WELLBUTRIN (bupropion HCl) Immediate-Release
Tablet &
WELLBUTRIN SR (bupropion HCl) Sustained-Release Tablets
[October 2 & 22, 2002: GlaxoSmithKline]
[Other labeling changes not in 2002 PDR: http://www.fda.gov/medwatch/SAFETY/2002/jun02.htm#wellbu]
Wellbutrin SR & Wellbutrin Label
CONTRAINDICATIONS
[Moved from WARNINGS]
(WELLBUTRIN & WELLBUTRIN SR) [are] contraindicated in patients undergoing abrupt discontinuation of alcohol or sedatives (including benzodiazepines).
PRECAUTIONS
Information for Patients:
Patients should be told that the excessive use or abrupt discontinuation of alcohol or sedatives (including benzodiazepines) may alter the seizure threshold. Some patients have reported lower alcohol tolerance during treatment with (WELLBUTRIN & WELLBUTRIN SR) Patients should be advised that the consumption of alcohol should be minimized or avoided.
Drug Interactions:
Levodopa and Amantadine: Limited clinical data suggest a higher incidence of adverse experiences in patients receiving bupropion concurrently with either levodopa or amantadine. Administration of (WELLBUTRIN & WELLBUTRIN SR) Tablets to patients receiving either levodopa or amantadine concurrently should be undertaken with caution, using small initial doses and gradual dose increases.
Drugs That Lower Seizure Threshold:
Alcohol: In post-marketing experience, there have been rare reports of adverse
neuropsychiatric events or reduced alcohol tolerance in patients who were drinking alcohol during treatment with (WELLBUTRIN & WELLBUTRIN SR) The consumption of alcohol during treatment with (WELLBUTRIN & WELLBUTRIN SR) should be minimized or avoided (also see CONTRAINDICATIONS).
Wellbutrin SR label
ADVERSE REACTIONS
Other Events Observed During the Clinical Development and Postmarketing Experience of Bupropion:
Nervous System: hallucinations- added
The Patient Information insert has been updated to reflect the labeling revisions above regarding alcohol. Contact the company for a copy of the new labeling.
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[October 2, 2002: Mylan]
Patient Information About:
Zagam (sparfloxacin) 200 mg Tablets
This section contains important information about Zagam (sparfloxacin), and should be read completely before you begin treatment. This section does not take the place of discussions with your health care professional about your medical condition or your treatment. This section does not list all benefits and risks of Zagam. The medicine described here can be prescribed only by a licensed health care professional. If you have any questions about Zagam talk with your health care professional. Only your health care professional can determine if Zagam is right for you.
What is Zagam?
Zagam is an antibiotic used to treat lung infections caused by certain germs called bacteria. Zagam kills many of the types of bacteria that can infect the breathing airways and lungs and has been shown in a large number of clinical trials to be safe and effective for the treatment of bacterial infections. Zagam Tablets are white and contain 200 mg of active drug.
Sometimes viruses rather than bacteria may infect the air passages and lungs (for example the common cold). Zagam, like all other antibiotics, does not kill viruses. Your health care professional can help determine whether your symptoms are caused by bacteria and whether Zagam is right for you.
How and When Should I Take Zagam?
Take two tablets of Zagam on the first day, then one tablet once a day for 9 additional days for a total treatment of 10 days. Zagam may be taken with or without food, with a full glass of water, preferably at the same time each day.
In order to make sure that all bacteria are killed and that your symptoms do not recur, you should complete the full course of medication. Do not take more than the prescribed dose of Zagam. If you miss a dose by mistake, do not take a double dose. If it is almost time for your next dose, skip the missed dose and take your regular dose on schedule.
Call your health care professional for instructions if you are not sure what to do.
You should contact your health care professional if you think your condition is not improving while taking Zagam.
Who should not take Zagam?
You should not take Zagam if you have ever had a severe allergic reaction to any of the group of antibiotics known as "quinolones" such as ciprofloxacin or levofloxacin.
You should not take Zagam if you have ever had severe sunburn when receiving other medications known to cause sensitivity to sunlight. While taking Zagam and for 5 days after the treatment is stopped, avoid exposure to the sun and sunlamps even when indoors. Phototoxic reactions can occur in patients exposed to shaded or diffuse light, such as through glass or during cloudy days.
You should not take Zagam if your daily activities or occupation entails sun exposure, or if you cannot suspend these activities as required for treatment with Zagam.
You should avoid Zagam if you have a rare condition known as congenital prolongation of the QT interval. If any of your family members have this condition you should inform your health care professional. You should avoid Zagam if you are being treated for heart rhythm disturbances with certain medicines such as disopyramide, quinidine, procainamide, amiodarone or sotalol. Inform your health care professional about all other medications you are taking, especially if you are taking a heart rhythm drug.
You should also avoid Zagam if the amount of potassium in your blood is low. Low potassium can sometimes be caused by medicines called diuretics such as furosemide and hydrochlorothiazide. If you are taking a diuretic medicine you should speak with your health care professional.
If you are pregnant or planning to become pregnant while taking Zagam, talk to your health care professional before taking the medication. Zagam is not recommended for use during pregnancy or nursing, as the effects on the unborn child or nursing infant are unknown.
Zagam is not recommended for children.
What are the possible side effects of Zagam?
Zagam is generally well tolerated. The most common side effects caused by Zagam, which are usually mild, include skin sensitivity to sunlight, diarrhea, nausea, headache, indigestion, dizziness, insomnia, abdominal pain, itching, altered taste, vomiting, and flatulence. You should be careful about driving or operating machinery until you are sure Zagam is not causing dizziness. If you notice any side-effects not mentioned in this leaflet or you have concerns about the side effects you are experiencing, please inform your health care professional.
In some people, Zagam, as with some other antibiotics, may produce a small effect on the heart that is seen on an electrocardiogram test. This could result in rare cases of abnormal heartbeat which may be dangerous. Contact your health care professional if you develop heart palpitations (fast beating), or have fainting spells.
Quinolone antibiotics including Zagam have been infrequently associated with ruptures of shoulder, hand, or Achilles tendons. If you develop pain, swelling, or rupture of a tendon you should stop taking Zagam and contact your health care professional.
Convulsions have been infrequently reported in patients receiving quinolone antibiotics including Zagam. If you have experienced convulsions in the past, be sure to let your health care professional know.
Quinolone antibiotics including Zagam have been infrequently associated with allergic reactions, even after just one dose. If you develop hives, skin rash, or other symptoms of an allergic reaction, you should stop taking this medication and call your health care professional.
If you experience any skin itching, rash, redness, burning or blister formation, or if you experience dizziness or light headedness, IMMEDIATELY STOP taking Zagam and call your health care professional right away.
Which medicines should not be taken with Zagam?
Zagam should not be taken with certain medicines used to treat an abnormal heartbeat.
These include quinidine, procainamide, amiodarone, and sotalol.
Some medicines also produce an effect on the electrocardiogram test, including cisapride, erythromycin, some antidepressants and some antipsychotic drugs. These may increase the risk of heart beat problems when taken with Zagam. For this reason it is important to let your health care professional know all of the medicines that you are using.
Some medications including antacids, sucralfate, multivitamins, supplements containing iron, zinc and calcium, may interfere with the absorption of Zagam. If you take these products, you should take them 4 hours after your Zagam dose.
Remember
Take two tablets of Zagamon the first day then once a day to complete 10 days.
Complete the course of medication even if you are feeling better.
Avoid exposure to the sun and sunlamps or tanning booths while taking Zagam and 5 days after treatment is stopped. Cover as much of your skin with clothing when brief exposure to the sun cannot be avoided.
Keep this medication out of the reach of children.
This information does not take the place of discussions with your health care professional about your medical condition or your treatment.
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ZIAGEN (abacavir sulfate) Tablets and Oral Solution
[October 2, 2002: GlaxoSmithKline]
ADVERSE REACTIONS
Hypersensitivity Reaction:
Fourth, fifth and sixth paragraphs -
In clinical studies, approximately 5% of adult and pediatric patients receiving ZIAGEN developed a hypersensitivity reaction. This reaction is characterized by the appearance of symptoms indicating multi-organ/body system involvement. Symptoms usually appear within the first 6 weeks of treatment with ZIAGEN, although these reactions may occur at any time during therapy. Frequently observed signs and symptoms include fever, skin rash, fatigue, and gastrointestinal symptoms such as nausea, vomiting, diarrhea, or abdominal pain. Other signs and symptoms include malaise, lethargy, myalgia, myolysis, arthralgia, edema, pharyngitis, cough, abnormal chest x-ray findings (predominantly infiltrates, which can be localized), dyspnea, headache, and paresthesia. Some patients who experienced a hypersensitivity reaction were initially thought to have acute onset or worsening respiratory disease. The diagnosis of hypersensitivity reaction should be carefully considered for patients presenting with symptoms of acute onset respiratory diseases, even if alternative respiratory diagnoses (pneumonia, bronchitis, pharyngitis, or flu-like illness) are possible.
Physical findings include lymphadenopathy, mucous membrane lesions (conjunctivitis and mouth ulcerations), and rash. The rash usually appears maculopapular or urticarial but may be variable in appearance. There have been reports of erythema multiforme. Hypersensitivity reactions have occurred without rash.
Laboratory abnormalities include elevated liver function tests, increased creatine phosphokinase or creatinine, and lymphopenia. Anaphylaxis, liver failure, renal failure, hypotension, adult respiratory distress syndrome, respiratory failure, and death have occurred in association with hypersensitivity reactions. Symptoms worsen with continued therapy but often resolve upon discontinuation of ZIAGEN.
Observed During Clinical Practice:
Skin: Suspected Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported in patients receiving abacavir primarily in combination with medications known to be associated with SJS and TEN, respectively. Because of the overlap of clinical signs and symptoms between hypersensitivity to abacavir and SJS and TEN, and the possibility of multiple drug sensitivities in some patients, abacavir should be discontinued and not restarted in such cases.
There have also been reports of erythema multiforme with abacavir use.
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ZINECARD (dexrazoxane) Injection
[October 31, 2002: Pharmacia & Upjohn]
CLINICAL PHARMACOLOGY
Special Populations: Pediatric: The pharmacokinetics of ZINECARD have not been evaluated in pediatric patients.
Gender: Analysis of pooled data from two pharmacokinetic studies indicate that male patients have a lower mean clearance value than female patients (110 ml/min/m 2 versus 133 ml/min/m 2 ). This gender effect is not clinically relevant.
Renal insufficiency: The pharmacokinetics of ZINECARD have not been evaluated in patients with renal impairment.
Hepatic insufficiency: The pharmacokinetics of ZINECARD have not been evaluated in patients with hepatic impairment. The ZINECARD dose is dependent upon the dose of doxorubicin (see Dosage and Administration). Since a doxorubicin dose reduction is recommended in the presence of hyperbilirubinemia, the ZINECARD dosage is proportionately reduced in patients with hepatic impairment.
PRECAUTIONS
Geriatric Use
Clinical studies of ZINECARD did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, elderly patients should be treated with caution due to the greater frequency of decreased hepatic, renal, or cardiac function, and concomitant disease or other drug therapy.
DOSAGE AND ADMINISTRATION
The recommended dosage ratio of ZINECARD:doxorubicin is 10:1 (eg, 500 mg/m2 ZINECARD: 50 mg/m 2 doxorubicin). Since a doxorubicin dose reduction is recommended in the presence of hyperbilirubinemia, the ZINECARD dosage should be proportionately reduced (maintaining the 10:1 ratio) in patients with hepatic impairment. ZINECARD must be reconstituted with 0.167 Molar (M/6) Sodium Lactate Injection, USP, to give a concentration of 10 mg ZINECARD for each mL of sodium lactate. The reconstituted solution should be given by slow I.V. push or rapid drip intravenous infusion from a bag. After completing the infusion of ZINECARD, and prior to a total elapsed time of 30 minutes (from the beginning of the ZINECARD infusion), the intravenous injection of doxorubicin should be given.
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ZITHROMAX (azithromycin dihydrate) Tablets,
Capsules, Single Dose Pack, Oral Suspension, I.V.
[October 16, 2002: Pfizer]
[Other labeling information not in 2002 PDR: http://www.fda.gov/medwatch/SAFETY/2002/may02.htm#zithro,
http://www.fda.gov/medwatch/SAFETY/2002/jul02.htm#zithro]
ZITHROMAX (azithromycin dihydrate) Tablets, Capsules, Single Dose Pack, Oral Suspension
PRECAUTIONS
Geriatric Use
In multiple-dose clinical trials of oral azithromycin, 9% of patients were at least 65 years of age (458/4949) and 3% of patients (144/4949) were at least 75 years of age. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.
ZITHROMAX 250 mg tablets contain 0.9 mg of sodium per tablet.
ZITHROMAX 500 mg tablets contain 1.8 mg of sodium per tablet.
ZITHROMAX for oral suspension 100 mg/5 mL contains 3.7 mg of sodium per 5 mL of constituted solution.
ZITHROMAX for oral suspension 200 mg/5 mL contains 7.4 mg of sodium per 5 mL of constituted solution.
ZITHROMAX 600 mg tablets contain 2.1 mg of sodium per tablet. ZITHROMAX for oral suspension 1 gram single-dose packets contain 37.0 mg of sodium per packet.
Zithromax (azithromycin dihydrate) I.V.
PRECAUTIONS
Geriatric Use
In multiple-dose clinical trials of intravenous azithromycin in the treatment of community-acquired pneumonia, 45% of patients (188/414) were at least 65 years of age and 22% of patients (91/414) were at least 75 years of age. No overall differences in safety were observed between these subjects and younger subjects in terms of adverse events, laboratory abnormalities, and discontinuations. Similar decreases in clinical response were noted in azithromycin- and comparator-treated patients with increasing age.
ZITHROMAX (azithromycin for injection) contains 114 mg (4.96 mEq) of sodium per vial. At the usual recommended doses, patients would receive 114 mg (4.96 mEq) of sodium. The geriatric population may respond with a blunted natriuresis to salt loading. The total sodium content from dietary and non-dietary sources may be clinically important with regard to such diseases as congestive heart failure.
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[October 18, 2002: Merck]
[Other labeling changes not in 2002 PDR: http://www.fda.gov/medwatch/SAFETY/2002/mar02.htm#zocor,
http://www.fda.gov/medwatch/SAFETY/2002/may02.htm#zocor]
Labeling provides for the addition of an indication for the treatment of heterozygous familial hypercholesterolemia in a new population of adolescent boys and girls at least one year postmenarchal, ages 10 to 17 years, with a recommended dosing range of 10 to 40 mg once daily of Zocor (simvastatin) tablets. Contact the company for a copy of the new labeling/package insert.
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ZOMIG & ZOMIG-ZMT (zolmitriptan) Tablets
[October 9, 2002: AstraZeneca]
ADVERSE REACTIONS
Post-Marketing Experience:
General: anaphylaxis or anaphylactoid reaction
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ZONEGRAN (zonisamide) Capsules
[October 7, 2002: Dainippon Pharmaceutical USA Corporation]
WARNINGS
Oligohidrosis and Hyperthermia in Pediatric Patients: Oligohidrosis, sometimes resulting in heat stroke and hospitalization, is seen in association with zonisamide in pediatric patients.
During the pre-approval development program in Japan, one case of oligohidrosis was reported in 403 pediatric patients, an incidence of 1 case per 285 patient-years of exposure. While there were no cases reported in the US or European development programs, fewer than 100 pediatric patients participated in these trials.
In the first 11 years of marketing in Japan, 38 cases were reported, an estimated reporting rate of about 1 case per 10,000 patient-years of exposure. In the first year of marketing in the US, 2 cases were reported, an estimated reporting rate of about 12 cases per 10,000 patient-years of exposure. These rates are underestimates of the true incidence because of under-reporting. There has also been one report of heat stroke in an 18-year-old patient in the US.
Decreased sweating and an elevation in body temperature above normal characterized these cases. Many cases were reported after exposure to elevated environmental temperatures. Heat stroke, requiring hospitalization, was diagnosed in some cases. There have been no reported deaths.
Pediatric patients appear to be at an increased risk for zonisamide-associated oligohidrosis and hyperthermia. Patients, especially pediatric patients, treated with Zonegran should be monitored closely for evidence of decreased sweating and increased body temperature, especially in warm or hot weather. Caution should be used when zonisamide is prescribed with other drugs that predispose patients to heat-related disorders; these drugs include, but are not limited to, carbonic anhydrase inhibitors and drugs with anticholinergic activity.
The practitioner should be aware that the safety and effectiveness of zonisamide in pediatric patients have not been established, and that zonisamide is not approved for use in pediatric patients.
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ZYRTEC (cetirizine HCl) Tablets and Syrup
[October 21, 2002 Pfizer]
Labeling provides for the use of Zyrtec (cetirizine hydrochloride) Tablets and Syrup for the relief of symptoms associated with perennial allergic rhinitis in adults and children 6 months of age and older and for the treatment of the uncomplicated skin manifestations of chronic idiopathic urticaria in adults and children 6 months of age and older. Contact the company for a copy of the new label/package insert.
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