ACEON (perindopril erbumine) - DEPO-PROVERA (medroxyprogesterone acetate) - FAMVIR (famciclovir) - KYTRIL (granisetron HCl) - LOVENOX (enoxaparin sodium) - LUPRON DEPOT-PED (leuprolide acetate) - MAXZIDE (triamterene/hydrochlorothiazide) - NOROXIN (norfloxacin) - NORVASC (amlodipine besylate) - NORVIR (ritonavir) - OXYCONTIN (oxycodone HCl) - PERIDEX (chlorhexidine gluconate) - PROCARDIA XL (nifedepine) - ZOVIRAX (acyclovir)

INDICATIONS AND USAGE:

Revised with notation that ACE inhibitors have a lesser effect on blood pressure in black patients, and that black patients receiving ACE inhibitors have been reported to have a higher incidence of angioedema compared to non-blacks (see WARNINGS: Angioedema).

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PRECAUTIONS:

Pediatric Use (new subsection): "Safety and effectiveness in pediatric patients have not been established. See WARNINGS section 6."

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FAMVIR (famciclovir) Tablets
[January 13, 1997: SmithKline Beecham]

PRECAUTIONS:

Carcinogenesis, Mutagenesis, Impairment of Fertility: Carcinogenesis: Comments related to the "marginal increases in the incidence of subcutaneous tissue fibrosarcomas or squamous cell carcinomas of the skin" in rats and mice have been removed [see subsection in package insert].

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CLINICAL PHARMACOLOGY:

Pediatric Patients: Statement that the pharmacokinetics of granisetron have not been adequately studied in children has been replaced with "A pharmacokinetic study in pediatric cancer patients (2 to 16 years of age), given a single 40 mcg/kg intravenous dose of Kytril injection, showed that volume of distribution and total clearance increased with age. No relationship with age was observed for peak plasma concentration or terminal phase plasma half-life. When volume of distribution and total clearance are adjusted for body weight, the pharmacokinetics of granisetron are similar in pediatric and adult cancer patients."

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ADVERSE REACTIONS:

Ongoing Safety Surveillance: Added: "Other reports include: skin necrosis at the injection site, inflammatory nodules at the injection site, purpura, systemic allergic reactions, and thrombocythemia." (NB: Change appears in 1997 PDR).

CLINICAL PHARMACOLOGY:

Pharmacokinetics (new subsection) added [see subsection in package insert].

ADVERSE REACTIONS:

Postmarketing (new subsection): Section revised to include reports from postmarketing surveillance [see subsection in package insert].

(NB: Changes appear in 1997 PDR)

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MAXZIDE (triamterene/hydrochlorothiazide) Tablets
[January 10, 1997: Mylan]

PRECAUTIONS:

Carcinogenesis, Mutagenesis, Impairment of Fertility: subsection structure revised, with Carcinogenesis, Mutagenesis, and Impairment of Fertility specifically separated:

Carcinogenesis: A specific statement that long-term studies with Maxzide (triamterene/hydrochlorothiazide combination) have not been conducted replaces prior statement regarding evaluation of mutagenic or carcinogenic potential.

Triamterene: Prior statements that studies have not been performed to determine triamterene's carcinogenic or mutagenic potential, and that reproductive studies in rats at doses up to 30 times the human dose revealed no evidence of impaired fertility, have been replaced by a revised new sub-subsection that delineates the results of studies conducted under the auspices of the National Toxicology Program [see sub-subsection in package insert].

Hydrochlorothiazide: Revised to present data from rodent (mice and rats) studies in terms of Maximum Recommended Human Dose (MRHD) on a body-surface area basis, in addition to classifying the previously included mg/kg/day data in terms of MHRD on a body-weight basis [see sub-subsection in package insert].

Mutagenesis: A specific statement reiterates previous notation that studies of Maxzide (triamterene/hydrochlorothiazide combination) mutagenic potential have not been performed.

Triamterene (new sub-subsection): Results of mutagenesis studies that have been conducted are delineated [see sub-subsection in package insert].

Hydrochlorothiazide: Previously included information regarding mutagenesis studies now placed in this specific sub-subsection.

Impairment of Fertility: New statement: "Studies of the effects of Maxzide, the triamterene/ hydrochlorothiazide combination, or of triamterene alone on animal reproductive function have not been conducted."

Hydrochlorothiazide: Revised to present data from rodent (mice and rats) studies in terms of MRHD on a body-surface area basis, in addition to mg/kg/day MRHD data [see sub-subsection in package insert].

Pregnancy Category C: Pregnancy Category remains C.

Teratogenic Effects, Maxzide (new sub-subsection replacing Teratogenic Effects): While noting as before that animal reproductive studies with Maxzide have not been conducted, results of a One Generation Study in the rat using an approximated Maxzide composition have been added [see sub-subsection in package insert].

In addition, the following paragraph has been added: "The safe use of Maxzide in pregnancy has not been established since there are no adequate and well-controlled studies with Maxzide in pregnant women. Maxzide should be used during pregnancy only if the potential benefit justifies the risk to the fetus."

Triamterene: Revised to present data from rats studies in terms of MRHD on a body-surface area basis, and in specifically noting MRHD on a body-weight basis, revised previously included human dose data [see sub-subsection in package insert].

Hydrochlorothiazide: Revised to present data from rodent (mice and rats) studies in terms of MRHD on body-weight and body-surface area bases [see sub-subsection in package insert].

NB: Both Teratogenic Effects, Triamterene and Teratogenic Effects, Hydrochlorothiazide include previous notation that since animal reproductive studies are not always predictive of human response, Maxzide should be used during pregnancy only if clearly needed.

Nonteratogenic Effects: In statement that thiazides and triamterene cross the placental barrier and appear in cord blood, "of animals" removed. Pancreatitis added to delineated adverse reactions that have occurred in the adult (replacing "adults") that are possible hazards to the fetus if thiazides and triamterene (replacing "Maxzide") are used in pregnant women.

Nursing Mothers: Previous notation replaced by: "Thiazides and triamterene in combination have not been studied in nursing mothers. Triamterene appears in animal milk and this may occur in humans. Thiazides are excreted in human breast milk. If use of the combination drug product is deemed essential, the patient should stop nursing."

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NOROXIN (norfloxacin) Tablets
[January 15, 1997: Merck]

CLINICAL PHARMACOLOGY:

Sentence regarding food and absorption revised: "The presence of food and dairy products may decrease absorption." (added words in italics)

PRECAUTIONS:

Information for Patients: Second patient advisement revised: "that norfloxacin should be taken at least one hour before or at least two hours after a meal or ingestion of milk and/or other dairy products." (italicized words have been added)

DOSAGE AND ADMINISTRATION:

First sentence revised: "Noroxin tablets should be taken at least one hour before or at least two hours after a meal or ingestion of milk and/or other dairy products." (italicized words have been added)

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NORVASC (amlodipine besylate) Tablets
[January 8, 1997: Pfizer]

ADVERSE REACTIONS:

Statement added: "The following postmarketing event has been reported infrequently where a causal relationship is uncertain: gynecomastia."

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NORVIR (ritonavir) Oral Solution and Capsules
[January 8, 1997: Abbott]

WARNINGS:

Addition of the following statements:

"Hepatic transaminase elevations exceeding 5 times the upper limit of normal, clinical hepatitis, and jaundice have occurred in patients receiving Norvir alone or in combination with other antiretroviral drugs (see Table 5). There may be an increased risk for transaminase elevations in patients with underlying hepatitis B or C. Therefore, caution should be exercised when administering Norvir to patients with pre-existing liver diseases, liver enzyme abnormalities, or hepatitis.

"There have been postmarketing reports of hepatic dysfunction, including some fatalities. These have generally occurred in patients taking multiple concomitant medications and/or with advanced AIDS. A definitive causal relationship has not been established."

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OXYCONTIN (oxycodone HCl) Controlled Release Tablets 80 mg
[January 6, 1997: Purdue Pharma L.P.]

PRECAUTIONS:

Special Precautions Regarding Oxycontin 80 mg Tablets (new subsection) : "OxyContin 80 mg tablets are for use only in opioid tolerant patients requiring daily oxycodone equivalent dosages of 160 mg or more. Care should be taken in the prescription of this tablet strength. Patients should be instructed against use by individuals other than the patient for whom it was prescribed, as such inappropriate use may have severe medical consequences."

DOSAGE AND ADMINISTRATION:

Individualization of Dosage (new subsection): Special Instructions for OxyContin 80mg Tablets: Notation that these are for use in opioid tolerant patients only with above paragraph restated.

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PERIDEX (chlorhexidine gluconate 0.12%) Oral Rinse
[January 8, 1997: Procter and Gamble]

CONTRAINDICATIONS:

Addition of or other formula ingredients to existing statement.

WARNINGS:

Statement referring to rare hypersensitivity and generalized allergic reactions has been deleted. New statement added: "Hypersensitivity and generalized allergic reactions have occurred. See CONTRAINDICATIONS."

PRECAUTIONS:

General: Point 3: Regarding alteration in taste, statement "Most patients accommodate to this effect with continued use of Peridex", has been deleted.

Statement "No instances of permanent taste alteration due to Peridex have been reported." has been revised to read: "Rare instances of permanent taste alteration following Peridex use have been reported via postmarketing product surveillance."

Usage in Pregnancy: Entire subsection deleted and replaced with "Pregnancy: Teratogenic Effects: Pregnancy Category B. Reproduction studies have been performed in rats and rabbits at chlorhexidine gluconate doses up to 300md/kg/day and 40 mg/kg/day, respectvely, and have not revealed evidence of harm to the fetus. However, adequate and well-controlled studies in pregnant women have not been done. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed."

Carcinogenesis, Mutagenesis, and Impairment of Fertility (replaces prior Carcinogenesis, Mutagenesis subsection): Revised with a more accurate statement reflecting the actual results of the rat study and addition of information regarding impaired fertility. (See complete subsection in package insert.)

ADVERSE REACTIONS:

Statement that no serious systemic adverse reactions associated with use of Peridex were observed in clinical testing has been deleted. The following statements replace previous statements regarding minor irritation , superficial desquamation, and transient parotitis:

"Oral irritation and local allergy-type symptoms have been spontaneously reported as side effects associated with use of chlorhexidine gluconate rinse. The following oral mucosal side effects were reported during placebo-controlled adult clinical trials: aphthous ulcer, grossly obvious gingivitis, trauma, ulceration, erythema, desquamation, coated tongue, keratinization, geographic tongue, mucocele, and short frenum. Each occurred at a frequency of less than 1.0%.

"Among postmarketing reports, the most frequently reported oral mucosal symptoms associated with peridex are stomatitis, gingivitis, glossitis, ulcer, dry mouth, hypesthesia, glossal edema, and paresthesia.

"Minor irritation and superficial desquamation of the oral mucosa have been noted in patients using Peridex.

There have been cases of parotid gland swelling and inflammation of the salivary glands (sialadenitis) reported in patients using Peridex."

DOSAGE AND ADMINISTRATION:

Statement added that "Patients should be instructed to not rinse with water, or other mouthwashes, brush teeth, or eat immediately after using Peridex."

BOTTLE LABEL:

What to Expect When Using Peridex: Statement "After treatment with Peridex has ended, taste perception will be normal." has been deleted. Statement "Spit out after use, Peridex should not be swallowed." has been added. Hypersensitivity now characterized as local rather than the previously used "rare".

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PROCARDIA XL (nifedipine)
[January 8, 1997: Pfizer]

ADVERSE REACTIONS:

Gynecomastia added to the list of adverse experiences reported in less than 1% of patients where a causal relationship is uncertain.

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ZOVIRAX (acyclovir) Capsules, Suspension, and Tablets
[January 8, 1997: Glaxo Wellcome]

Capsules, Tablets, and Suspension

ADVERSE REACTIONS:

Observed During Clinical Practice: Nervous: Seizure added to list of adverse reactions (NB: Change appears in 1997 PDR).

Ointment 5%

PRECAUTIONS:

Pediatric Use (new subsection): "Safety and effectiveness in pediatric patients have not been established."

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