MARCH 2002

FORMULARY ADDITIONS

Tenofovir Disoproxil Fumarate

Viread® (Gilead Sciences, Inc.)

300 mg Tablets

Tenofovir disoproxil fumarate (DF) is indicated in combination with other antiretrovirals for the treatment of HIV-1 infection. Studies were conducted in treatment experienced adults with evidence of HIV-1 viral replication while receiving antiretroviral treatment. Studies in treatment-naïve patients are ongoing and the risk-benefit for this population has yet to be determined.

A black box warning that accompanies prescribing information states that lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs alone or in combination with other antiretrovirals. A majority of these cases have been in women. Obesity and prolonged nucleoside exposure are risk factors. Particular caution should be exercised when administering nucleoside analogs to any patient with known risk factors for liver disease; however, cases have also been reported in patients with no known risk factors. Treatment with tenofovir should be stopped in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity (including hepatomegaly and steatosis even in the absence of marked transaminase elevations).

Tenofovir DF should not be administered to patients with a creatinine clearance <60 ml/min until data becomes available describing the disposition of tenofovir in these patients. Because tenofovir is not entirely renally excreted (renal clearance=70-80%), pharmacokinetics may be altered in patients with hepatic insufficiency.

The most common adverse events that occurred were moderate gastrointestinal event such as nausea, vomiting, and flatulence.

Based on the results of in vitro experiments and the known elimination pathway of tenofovir, the potential for CYP450 mediated interactions involving tenofovir with other medicinal products is low.

Co-administration of tenofovir with other drugs that are eliminated by active tubular secretion may increase serum concentrations of either tenofovir or of the co-administered drug due to competition of the elimination pathway. Drugs that decrease renal function may also increase serum concentration of tenofovir.

Other drugs that have affected tenofovir peak concentration have included indinavir (increase by 14%) and lopinavir/ritonavir (increased by 31%). Tenofovir affects peak concentration of didanosine (increase by 28%), lamivudine (decrease by 24%), indinavir (decreased by 11%), and lopinavir/ritonavir (decrease by 28%). Tenofovir had no effect on efavirenz onset.

DRUG AND FOOD INTERACTIONS: Administration of tenofovir following a high fat meal increases the AUC by 40% and the C_maxby approximately 14%. Food delays the time to C_maxby approximately one hour. Tenofovir should be taken with a meal to enhance its bioavailability.

DOSAGE AND ADMINISTRATION: The dose of tenofovir is 300 mg once daily taken orally with a meal. If given with didanosine, tenofovir should be administered two hours before or one hour after didanosine. If overdose occurs, the patient must be monitored for evidence of toxicity and standard supportive treatment given as necessary. It is not known whether peritoneal or hemodialysis increases the rate of elimination of tenofovir.

Polyethylene Glycol 3350, NF Powder for Solution

Miralax^® (Braintree Laboratories, Inc.)

17 Gram Packets

Polyethylene glycol 3350 (Miralax^®) powder for oral solution is an osmotic laxative indicated in the treatment of constipation. Miralax appears to have no effect on the balance of electrolytes and is not associated with tachyphylaxis.

In patients who are not constipated, Miralax is completely recovered. However, in constipated patients, Miralax recovery is incomplete and highly variable. Miralax is not fermented into hydrogen or methane by colonic microflora in human feces. There is no systemic absorption with oral administration. Onset of effect occurs in two to four days.

Miralax is contraindicated in patients with known or suspected bowel obstruction and in patients who are hypersensitive to polyethylene glycol. Patients with symptoms suggestive of bowel obstruction (nausea, vomiting, abdominal pain or distention) should be evaluated to rule out obstruction before Miralax is initiated. All patients who present with complaints of constipation should have a complete medical exam to detect associated metabolic, endocrine, and neurogenic conditions. In addition, patients should be questioned about any medications they may be taking in order to rule out medication-induced constipation. Patients should be educated about good defacatory and eating habits (such as high fiber diet and plenty of fluids) and lifestyle changes (regular exercise) which may be helpful to produce more regular bowel habits.

Nausea, abdominal bloating, cramping, and flatulence have been reported to occur with the use of Miralax. High doses may produce diarrhea and excessive stool frequency. The elderly are more susceptible to diarrhea as this has occurred in this patient population at the normal recommended dose of 17 grams.

DRUG INTERACTIONS: No specific drug interactions have been identified.

DRUG AND FOOD INTERACTIONS: Miralax must be mixed with water, juice, soda, coffee, or tea prior to administration. The manufacturer’s prescribing information lists no drug/food interactions.

DOSAGE AND ADMINISTRATION: The usual adult dose for Miralax is one 17gm packet day per day in eight ounces of water, juice, soda, coffee, or tea. Approximately two to four days may be required to produce a bowel movement. The safety and effectiveness of Miralax has not been established in pediatric patients.

PREGNANCY: Category C. Animal reproductive studies have not been performed with Miralax. It is not known whether this medication can cause fetal harm when administered to pregnant women or if it can effect reproductive capacity. Administer with caution only when clearly needed.

Formulary Additions and Deletions Not Listed in 2001-2002 Formulary Publication
Generic Name	Trade Name	Therapeutic Class	Action	Date	Comments
Amphotericin B Suspension	Fungizone	Antifungal	Deleted	1/8/02	Discontinued by manufacturer
Cefuroxime Axetil Suspension	Ceftin Suspension	Second Generation Cephalosporin	Added	3/13/01
Chloramphenicol Ophthalmic Ointment 1%	Chloromycetin	Ophthalmic Antibiotic	Deleted	3/4/02
Colchicine 0.5mg	Colchicine	Antigout	Deleted	1/22/02
Colchicine 0.6mg	Colchicine	Antigout	Added	1/2202
Crotalide Polyvalent Immune Fab (Ovine)	Crofab	Crotalid antivenin	Added	11/27/01
Darbepoetin alfa	Aranesp	Colony stimulating factor	Added	11/27/01
Delavirdine	Rescriptor	NNRTI	Deleted	8/29/01
Desflurane	Suprane	Inhaled Anesthetic	Added	9/25/01
Didanosine	Videx IR	NRTI	Deleted	8/28/01
Didanosine	Videx EC	NRTI	Added	8/28/01
Divalproex Sodium	Depakote ER	Antimigraine	Added	6/27/01
Docusate Sodium with Casanthranol	Peri-Colace softgels	Stool softener/laxative	Added	5/3/01
Dofetilide	Tikosyn	Class III antiarrhythmic	Added	6/26/01	Restricted to cardiology
Drotrecogin alfa	Xigris	Recombinant human activated protein C for severe sepsis	Added	11/27/01	Restricted by protocol
Fluticasone with Salmeterol for Inhalation	Advair	Antiasthmatic	Added	6/22/01
Hyaluronidase	Wydase	Extravasation antidote	Deleted	7/19/01	Discontinued by manufacturer
Insulin Glargine	Lantus	Insulin	Added	9/25/01
Lactobacillus GG	Culturelle	Dietary Supplement	Added	9/25/01
Lidocaine 4%	Ela-Max	Topical anesthetic	Added	9/25/01
Lomefloxacin	Maxaquin	Antibiotic	Deleted	3/4/02
Lopinavir/Ritonavir	Kaletra	Protease inhibitor	Added	8/28/01
Loxapine Injection	Loxitane	Antipsychotic	Deleted	8/01/01
Metoprolol Succinate	Toprol XL	Antihypertensive	Added	5/3/01
Niacin 100mg tablet	Niaspan	Vitamin	Added	3/4/02
Ofloxacin	Floxin	Antibiotic	Deleted	3/4/02
Oxcarbazepine	Trileptal	Antiepileptic	Added	2/27/01
Oxybutynin XL	Ditropan XL	Urinary Antispasmodic	Added	2/27/01
Pantoprazole IV	Protonix	Proton pump inhibitor	Added