Combination Products
Brand
Name Active Ingredients Normal Adult Dosage Atripla Efavirenz 600 mg,
Emtricitabine 200 mg, Tenofovir 300 mg
1 PO qd
Combivir Zidovudine 300 mg, Lamivudine 150 mg
1 PO bid Epzicom Abacavir 600 mg,
Lamivudine 300 mg
1 PO qd Trizivir Zidovudine 300 mg,
Lamivudine 150 mg, Abacavir 300 mg
1 PO bid
Truvada Tenofovir 300 mg, Emtricitabine 200 mg
1 PO qd
h. Hepatitis, intracranial hemorrhage (tipranavir, boxed warning) i. Nephrolithiasis (indinavir) (iv) Drug interactions
a. St. John’s wort reduces activity of all PI and should be avoided.
b. PI agents exhibit complicated drug interaction profiles and drug interactions should be reviewed for each specific agent with proper drug information resources. Ritonavir is an especially potent inhibitor of CYP isoenzymes.
(d) Nucleotide inhibitors (i) Tenofovir (Viread)
a. Mechanism of action: competitively inhibits HIV reverse transcriptase and causes chain termination after incorporation into DNA
b. Used in combination with other antiretrovirals for HIV-1 suppression (ii) Adefovir (Hepsera)
a. Mechanism of action: Competitively inhibits HBV DNA polymerase and results in chain termination after incorporation into viral DNA b. Used for hepatitis B, not for HIV c. Adverse effects: nephrotoxicity (e) Fusion inhibitors: Enfuvirtide (Fuzeon)
(i) Mechanism of action: binds to gp41 subunit and prevents conformational changes for fusion
(ii) Dosage: 90 mg SC bid (iii) Adverse effects: injection site
reactions, fever, flu like symptoms.
May cause allergic reactions.
(f) Entry inhibitor: Maraviroc (Selzentry) (i) Mechanism of action: Blocks CCR5
receptor, one of the receptors HIV uses to enter its target cell; prevents infection of the cell
(ii) Used in treatment-experienced patients (iii) Adverse effects: Cough, rash, dizziness.
May cause liver toxicity (boxed warning), allergic reaction
(g) Integrase inhibitor: Raltegravir (Isentress) (i) Mechanism of action: Interferes with
integrase, a viral enzyme responsible for replication
(ii) Used in treatment-experienced patients with documented resistant strains and perguidelines can be used first line treatment in naive patients (iii) Adverse effects: Nausea, diarrhea,
headache. May cause myopathy and rhabdomyolysis.
2. Treatment of specialized circumstances resulting in HIV exposure
a. Vertical transmission, also known as mother-to-child transmission
(1) Two drugs effective as monotherapy to prevent perinatal transmission
(a) Zidovudine (b) Nevirapine
b. Postexposure prophylaxis (HIV-PEP) (1) Basic regimens
(a) Zidovudineþ lamivudine (available as Combivir)
(b) Zidovudineþ emtricitabine (c) Tenofovir DFþ lamivudine (d) Tenofovir DFþ emtricitabine
(available as Truvada) (i) Alternative regimens
a. Lamivudineþ stavudine b. Emtricitabineþ stavudine c. Lamivudineþ didanosine (2) Expanded regimens consist of one of the
following
(a) Lopinavir/ritonavir (Kaletra) (b) Atazanavirþ ritonavir (c) Fosamprenavirþ ritonavir (d) Indinavirþ ritonavir (e) Saquinavirþ ritonavir (f) Nelfinavir
(g) Efavirenz
(3) Antiretrovirals NOT generally recommended for prophylaxis (a) Nevirapine
(b) Delavirdine (c) Abacavir (d) Zalcitabine
References
1. Depiro J: Pharmacotherapy: A pathophysiological approach, ed 7, McGraw-Hill Medical, 2008.
2. AIDS info, Clinical Guidelines Portal. US Department of Health and Human Services. Available at: http://
www.aidsinfo.nih.gov/guidelines. (Accessed Feb 2, 2010)
PATIENT PROFILE
Patient Initials: KT Sex: Male
Age: 33 years Height: 501000 Weight: 64 kg Race: Latin American Allergies: Penicillin (rash)
Chief Complaint/History: None. Patient goes to clinic pharmacy today for new highly active antiretroviral therapy prescriptions; recently HIV regimen changed due to HIV viral load studies and decreasing CD4 counts. Reyataz and Truvada are new prescriptions.
Medical History:
Diagnosed with HIV in 2001
Episode of Pneumocystis pneumonia (PCP) in 2006 Significant laboratories at last medical appointment:
CD4þ cell count: 150 per mm3(was>200 cells/mm3 6 months ago)
Social History:
Tobacco use: 1 pack-per-day until 2002; none currently Alcohol use: 1 glass of wine or a beer with dinner several
times per week Medications:
Truvada 1 tablet PO q day (new)
Reyataz 150 mg, 2 capsules PO q day (new) Norvir 100 mg, 1 capsule PO q day
Therapeutic multivitamin with minerals PO once per day
PATIENT PROFILE QUESTIONS
1. When dispensing Norvir capsules to KT, which of the following apply?
I. If stored at room temperature, the patient should discard the capsules after 60 days.
II. The capsules are best stored refrigerated.
III. The capsules should be dispensed in the original container.
a. I only b. II only c. III only d. I and III e. II and III
Answer: b. If Norvir is stored at room temperature, the capsules should be discarded after 30 days, not 60 days. There is no requirement to dispense the capsules in the original container. Preferably, the capsules are stored under refrigeration.
2. Based on current CD4 counts, the practitioner decides that a PCP prophylaxis regimen should be initiated. Which of the following is considered the first-line regimen for prophylaxis of PCP?
a. Dapsone 100 mg PO every day b. Bactrim DS 1 tablet PO every day c. Atovaquone 750 mg PO twice daily
Answer: b. The combination of sulfamethoxazole (SMZ) with trimethoprim (TMP) is considered first line for PCP prophylaxis. Numerous trials have indicated its effectiveness; patients taking SMZ-TMP regimens have approximately a 5% chance of developing PCP. SMZ-TMP treatment may also prevent other infections, such as toxoplasmosis.
PCP prophylaxis is usually started when CD4 counts are lower than 200, as is the case with KT’s most recent laboratories. The other regimens are acceptable alternatives; however, atovaquone is expensive, and is not always recommended by organizations that govern guidelines for patients with HIV.
3. Appropriate counseling regarding how KT should take the Reyataz in the antiviral regimen include which of the following?
I. Take at the same time as Norvir.
II. Take on an empty stomach, 2 hours before a meal.
III. Take with food.
IV. Take at the same time as Truvada.
a. I only b. II only c. III only d. II and IV e. I and III
Answer: e. To reach appropriate serum concentrations for efficacy in this triple drug antiretroviral regimen, Reyataz (atazanavir) is
“boosted” with Norvir (ritonavir), and the two drugs are best taken at the same time to accomplish this.
Also, Reyataz is taken with food for best absorption.
The patient should be counseled with regard to optimal drug administration and compliance.
4. Which of the following are the most common side effects for Truvada?
I. Diarrhea, nausea, headache, strange dreams, sleeping problems
II. Lipodystrophy III. Lactic acidosis IV. Liver problems a. I and II
b. II and III c. III and IV
Answer: a. Lipodystrophy (change in distribution of body fat) is a common side effect with longer use of antiretroviral medications such as Truvada
(emtricitabine, tenofovir). The side effects listed in I are the most common patients notice. Lactic acidosis, liver problems (steatosis and hepatomegaly), kidney problems, or pancreatitis are potential serious side effects of this drug combination that are less common.
REVIEW QUESTIONS
(Answers and Rationales on page 363.)
1. A 21-year-old, HIV-positive man presents to the HIV clinic for examination. A PPD is placed, and when he returns to clinic 3 days later, is found to be positive.
His LFTs are normal, and he is begun on anti-TB therapy. In addition to clinical evaluation for adverse events, what is the most appropriate monitoring regimen?
a. Only clinical examination and interview is needed b. Measure LFT monthly
c. Measure LFT every 8 weeks d. Measure LFT at 2, 4, and 6 weeks e. None of the above
2. Which of the following are non-nucleoside reverse transcriptase inhibitors?
I. Ganciclovir II. Nevirapine III. Efavirenz a. I only b. III only c. I and II d. II and III e. I, II, and III
3. A 35-year-old HIV-positive woman goes to the urgent care clinic with complaints of genital herpes.
She reports parasthesias for 4 days and developed vesicular lesions on her labia this morning. The patient explains that this is her third outbreak in 6 months. What is the most appropriate therapy?
a. Valacyclovir, 1 g PO bid for 5 days b. Valacyclovir, 500 mg PO bid for 3 days c. Famciclovir, 500 mg PO qd for 5 days d. Acyclovir, 400 mg PO tid as continuous
suppressive therapy
e. Acyclovir, 400 mg PO tid for 3 days
4. A 30-year-old woman presents to the HIV clinic after diagnosis at another hospital. Laboratory evaluation reveals the following:
RPR: positive FTA-ABS: positive
Lumbar puncture: 70 WBC, normal protein, negative VDRL
The patient reports anaphylactoid reaction to penicillin several years ago. What is the most appropriate course of therapy?
a. Perform penicillin skin test followed by desensitization
b. Benzathine penicillin G 2.4 mU IM q week for 3 weeks
c. Benzanthine penicillin G 2.4 mU IM for one dose d. a and b
e. a and c
5. What statements are TRUE about protease inhibitors?
a. Ritonavir (Norvir), saquinavir (Invirase,
Fortovase) and indinavir (Crixivan) are examples of protease inhibitors
b. Protease inhibitors inhibit cytochrome P450 oxidations
c. Select antihistamines and benzodiazepines are contraindicated with protease inhibitors d. All of the above
e. None of the above
6. CO is a 35 year-old HIV-positive patient who is receiving HAART regimen. About a month after initiating therapy, he comes to the emergency department complaining of severe flank pain, frequent urination, and nausea. Which of the following drugs is the most likely cause of his symptoms?
a. Nevirapine b. Indinavir c. Didanosine d. Efavirenz e. Zidovudine
...
Kidney Disorders 16
CHAPTER
...
I. Background
A. The kidneys are responsible for removing toxins, chemicals, and waste products from the blood;
regulating acid concentration; and maintaining water and electrolyte balance in the body by excreting urine.
II. Common Types and Causes of Kidney Disorders A. Fanconi syndrome
1. Definition: The tubes in the kidneys do not work properly.
a) Unable to reabsorb glucose, amino acids, small proteins, water, calcium, potassium, magnesium, bicarbonate, and phosphate, making the blood overly acidic
b) May be caused by inherited disorders such as cystinosis, galactosemia, glycogen storage disease, hereditary fructose intolerance, Lowe syndrome, Wilson’s disease, tyrosinemia, medullary cystic disease, and vitamin D dependency;
exposure to heavy metals, certain drugs, chemicals (e.g., toluene), or dietary supplements (e.g., lysine); and may even result from kidney transplantation 2. Signs and symptoms
a) Increased urination, excessive thirst, dehydration, constipation, anorexia nervosa, vomiting, high levels of sugar, phosphate,
calcium, uric acid, amino acids, and protein in the urine, high levels of chloride and low levels of phosphate and calcium in the blood
3. Treatment
a) Replacement of fluids and nutrients lost in urine
b) Addition of sodium bicarbonate, a diuretic such as hydrochlorothiazide, and
supplementation with vitamin D and phosphate
B. Glomerulonephritis
1. Definition: an acute or chronic kidney disease that occurs when the kidneys are unable to properly remove waste and excess fluids from the body. This occurs when there is glomerular damage from immune or inflammatory
reactions and lesions.
2. It can occur by itself or in conjunction with other diseases such as lupus, Goodpasture syndrome, diabetes, immunoglobulin A (IgA) nephropathy, polyarteritis, Wegener
granulomatosis, or infection with streptococcus, HIV, hepatitis B or C
3. Signs and symptoms: dark-colored urine, foamy urine, high blood pressure, fluid retention that causes swelling, fatigue, and less-frequent urination
4. Treatment
a) The goal of treatment is to reduce the decline of kidney function and control blood pressure. Corticosteroids are often used to reduce kidney inflammation. Diuretics, angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor agonists (ARB), calcium channel blockers, or beta blockers may be used.
C. Focal segmental glomerulosclerosis (FSGS) 1. Definition: A type of glomerular disease that can
cause permanent kidney disease in children and adults by attacking the glomeruli, the tiny structures inside the kidneys where blood is filtered. The most common sign of FSGS is the nephrotic syndrome, which is characterized by fluid in the body tissues that causes swelling, excess protein in the urine, hypoalbuminemia, and high cholesterol.
2. Signs and symptoms
a) Fatigue, nausea, headache, foamy urine, weight gain, poor appetite, proteinuria Table 16-1