- Email: [email protected]
AIDS
Drug Interactions: How They Affect People Living With HIV/AIDS Margaret C. Dykeman, MS, RN, Rachael Wallace, RN, Pamela Ferrell, BSN, RN, John Jasek, BA, and Peter V. Tortorice, Pharm D.
Given the diversity and increasing life span of HIV-positive people, medical management of the associated complications is becoming more complex. This complexity is compounded by the growing number of drugs available to treat people with HIV/AIDS. Information regarding the adverse reactions and~or interactions of these drugs in combination is limited. The purpose of this paper is to review what is currently known about synergistic, antagonistic, and potentially toxic interactions. Included is a table containing side effects and interactions among drugs commonly used to treat clients with HIV/AIDS. K e y w o r d s : Drug interaction, HIV/AIDS,
nursing education
JANAC Vol.7, No. 4, July-August,1996
Margaret C. Dykeman, MS, RN, is a Nurse Associate~Nurse Epidemiologist,CookCounty HIV Primary CareCenter, Chicago.Rachael Wallace,RN, is a Nurse Manager, TriadHealth Practice/HIVTreatment Center, Illinois MasonicMedical Center, Chicago.Pamela Ferrell,BSN, RN, is HIV Coordinator, VA Westside Medical Center,Chicago.JohnJasek, BA, is a Data Manager, CookCounty HIV Primary CareCenter, Chicago. Peter V. Tortorice,Pharm D, is an Oncology Clinical Pharmacist,IllinoisMasonic Medical Center, Chicago. T h e complexity of pharmacologically treating a patient with HIV/AIDS is growing, as are the number of new drugs being prescribed. Due to these factors, the potential for drug interactions in this population is increasing rapidly. Sanford (1992) reported that drug interactions occur in 5% of patients taking only a few drugs; however, when clients concurrently receive 10 to 20 drugs, the frequency of interactions may increase to 20%. Drug interactions may be beneficial, but often they are potentially harmful and can contribute to increased morbidity and mortality. Matthewson-Kuhn (1994) states that 5%10% of all admissions to hospitals occur because of adverse drug reactions. HW/AIDS patients, particularly those with advanced disease are especially vulnerable to drug interactions for two reasons. First, people with late stage disease are commonly prescribed more than 10 medications concurrently. Second, many drugs being used are experimental, and little is known about their actions and interactions. Since nurses perform the majority of client teaching, they must continuously update their knowledge concerning the drugs they prescribe or administer to ensure that clients have the best information available on which to base their healthcare derisions. The purpose of this paper is to discuss several reasons why drugs, whether taken alone or in combination with other drugs, may have different effects than expected or desired. Table 1 lists the primary drugs most frequently used in the provision of HIV/AIDS care. Information 67
D r u g Interactions: H o w T h e y A f f e c t P e o p l e L i v i n g W i t h H I V / A I D S
provided in the table includes the drug name and classification; the most frequently noted adverse effects, including both side and toxic effects; and a list of drugs, that may interact with the primary drug when taken concurrently, with specific interactions. Often, management of the interaction is provided. Please note that when the interaction results in an increase or decrease in serum levels, the change refers to the serum level of the primary drug. The table is offered as a quick reference to nurses working in clinical areas and is not meant to be a complete reference. As previously noted, multiple drug therapy is probably the most frequent cause of adverse drug reactions. Penn (1980) defines an adverse drug reaction "as any response to a drug that is noxious and unintended, and which occurs at doses normally used in man" (pp. 3839). The desired therapeutic outcome for most drug therapy depends to a large extent upon reaching and maintaining an optimal level of the drug in the serum. If for some reason the serum level exceeds the optimal range, toxicity may become a problem. If the serum level is below therapeutic range, the patient may not achieve the intended effect of the medication. A number of different factors may alter the serum level of a drug and thus cause unwanted drug reactions. The coadministration of a second medication may lead to a d r u g i n t e r a c t i o n or i n c o m p a t i b i l i t y . Matthewson-Kuhn (1994) makes a distinction between the two. Drug incompatibilities occur when chemical or physical interactions between two drugs change the molecular structure of one or both drugs. A drug interaction alters one or both of the drugs' pharmacological effects due to an interaction between two drugs or drugs and food. The outcomes of incompatibilities and drug interactions are similar, for ~the purpose of this paper, the authors have treated them as being comparable. The interaction between two drugs being administered concurrently may cause increases or decreases in serum levels of one or both of the drugs. Changes in serum levels may be due to one drug altering the absorption, distribution, metabolism, or elimination of the other drug. Drug interactions also may occur because of similar pharmacodynamic properties, including similar toxicities.
68
Absorption Serum levels of drugs administered orally depend largely on how well the drug is absorbed in the gastrointestinal (GI) tract. Absorption along the GI tract can be altered by the ingestion of food, the administration of drugs that change pH levels in the gut or alter GI motility, by disease states, or by drug interaction.
Food Intake There is a clinically significant relationship between food intake and absorption of many of the commonly prescribed medications for people with AIDS. Food enhances the absorption of atovaquone, clofazimine, itraconazole and ketoconazole, which may increase the serum drug level. The absorption of azithromycin, didanosine, zalcitabine, zidovudine, ciprofloxacin, rifampin, and isoniazid is hindered by the presence of food in the stomach (Lor, 1994). A clinical example of the importance of managing food intake to enhance drug absorption is the protease inhibitor, saquinavir, which must be given with a large meal that is high in fat content. pH Level Many medications need an acidic environment for absorption. Acidity levels may be altered, either by bouts of vomiting or diarrhea--frequent complaints of many AIDS patients. Food in the gut or the administration of concurrent drugs such as antacids or H2 blockers also can alter the pH (Torres, 1994a). The concurrent administration of an antacid with a drug needing an acidic environment for absorption will s i g n i f i c a n t l y decrease the a m o u n t of d r u g being absorbed and thus decrease the serum level. For example, giving antacids at the same time as zalcitabine decreases the serum level of zalcitabine by 25% (Cheng, 1994). However, not all drugs work best in an acidic environment. For example, didanosine comes prepared with its own buffers because it can be absorbed only in
JANAC Vol.7, No. 4, July-August,1996
Table 1. Common Actions and Interactions of Drugs Used in the Treatment of HIV/AIDS Primary Drug/Class
Adverse Effects
Drugs Taken Concurrently
Interactions
Acyclovir (anti- viral)
Nausea, phlebitis, nephrotoxicity,
Probenecid
Increases serum levels, toxicity
Zidovudine
Increased drowsiness, lethargy
Intrathecal methotrexate
Increased risk of CNS side effects
Headache, malaise, myalgias, thrombophlebitis , nausea, vomiting, fever, chills, hypokalemia, anemia, nephrotoxicity,
Probenecid
May increase serum levels
Pentamidine, antineoplastics, amino glycosides, foscarnet
Increased risk of kidney toxicity
weight loss, hypotension, metabolic acidosis
Zidovudine, ganciclovir
Increased risk of bone marrow toxicity, anemia
Corticosteroids, synthetic penicillins
May increase risk of hypokalemia
Ketaconazole, fluconazole, itraconazole
May interfere with activity
Erythromycin, itraconazole, ketaconazole, fluconazole, clarithromycin, ritonavir, indinavir
May decrease metabolism
May result in lifethreatening arrhythmias; do not use concurrently
Food
May increase serum levels
Recommended to take with food
Highly protein- bound drugs such as aspirin or warfarin
Will compete with other highly proteinbound drugs
Documentation not proven at this time
Drowsiness, ataxia,
Isoniazid
Increased risk of hepatotoxicity, may decrease serum levels
Monitor serum levels
bone marrow depression with anemia, leokopenia, thrombocytopenia, vertigo, rashes, photosensitivity, fever, chills, hepatitis
Clarithromicin
May increase serum levels
Itraconazole, ketoconazole
May alter serum levels
Penicillin, rifampin
Decrease in serum level
Ritonavir
77% increase in serum level
headache, dizziness, seizures, diarrhea, vomiting, renal failure, serum creatine elevation, inflammation
Amphotericin B (anti- fungal)
Astemizole (anti- histamine)
Sedation, dizziness, dry mouth, cardiac dysfunction, headache, increased appetite, nausea, nervousness
Atovaquone (anti- protozoal)
Rash, nausea, diarrhea, headache, fever, insomnia, asthenia, liver dysfunction
Carbamazepine (anti- convulsant)
Clarithromycin (macrolide antibiotic)
Notes:
Headache, diarrhea, nausea, abnormal taste, dyspepsia, leukopenia, elevated prothrombin time
Comments
Monitor serum levels regularly
Italicized adverse effects are commonly observed; effects in bold are potentially life- threatening. Drug information inserts from a variety of pharmaceutical companies were used as additional references for the body of the table.
JANAC Vol.7, No. 4, July-August, 1996
69
Table 1. Continued Primary Drug/Class
Adverse Effects
Drugs Taken Concurrently
Interactions
Comments
Clincamycin (anti- bacterial)
Diarrhea, nausea, vomiting, abdominal pain, tenesmus, maculopapular rash, urticaria, pseudomembranous colitis (rare)
Erythromycin
In vitro antagonism between drugs
Not recommended for concurrent administration
Kaolin- pectin
May decrease absorption
Administer 2 hours apart
Zidovudine
Increased bone marrow toxicity
Administer 2 hours apart
Didanosine
Decreases absorption via increased gastric pH
Dapsone (anti- bacterial)
Acute hemolysis may occur with people who have g6pd deficiency, hemolysis of red blood cells with anemia, exfoliative dermatitis, peripheral neuropathy (rare) nausea, vomiting, abdominal pain, headache, abnormal liver function tests, rash, vertigo, blurred vision, insomnia
Didanosine, zalcitabine Pyrimethamine ( or other folinic acid antagonists)
May increase risk of peripheral neuropathy Increased risk of hemolysis
Rifampin May cause increased clearance / decreased serum level Trimethoprim Increase in serum level
Didanosine (anti- retroviral)
Myalgia, arthritis, insomnia, diarrhea, nausea, vomiting, rash and pruritis, pancreatitis, leukopenia, peripheral neuropathy, headache
Food in the stomach
May decrease absorption
Do not take with food
H2 blockers, antacids
May increase serum level
Ganciclovir, alcohol, pentamidine, zalcitabine
Similar toxicities, increased chance of pancreatitis
Ritonavir
13% decrease in serum level
Zalcitabine, stavudine alcohol, metronidazole, isoniazid, dapsone
Similar toxicities, increased chance of neuropathy
Ethambutol (anti- tubercular)
Retrobulbar neuritis, head'ache, dizziness,
Zalcitabine, stavudine dapsone, isoniazid
Increased risk of neurotoxicity
Fluconazole (anti- fungal)
Nausea, vomiting, peripheral neuropathy, pancreatitis, abdominal pain, dizziness, headache, hepatotoxicity (rare)
Hydrochlorothiazide
May increase serum level
Rifampin
May decrease serum level
70
No dosage adjustment required
JANAC Vol.7, No. 4, July-August, 1996
Table 1. Continued Primary Drug/Class
Adverse Effects
Drugs Taken Concurrently
Interactions
Foscarnet
Renal failure, anemia, fever, diarrhea,
Amphotericin B, aminoglycosides, cyclosporin
Increased risk of nephrotoxicity
Pentamidine
Life threatening hypocalcemia, nephrotoxidty
Zidovudine
Possible increased incidence of anemia
Zalcitabine, stavudine
Increased risk of nephrotoxicity and peripheral neuropathy
Antineoplastic agents, radiation therapy, zidovudine, dapsone, pentamidine, amphotericin B, trimethoprim/sulfam ethoxazole
Increased risk of bone marrow suppression
Nephrotoxic drugs (e.g., aminoglycosides)
Increased serum creatinine
Use concurrently with caution
Ketaconazole
Increased serum level
Consider reducing dose of indinavir to 600 mg three times daily
Rifampin
Decreased serum level
Co- administration not recommended
(anti- viral)
granulocytopenia, leukopenia, bone marrow suppression, headaches, seizures, nausea, vomiting, hypocalcemia, hypomagnesemia, hypokalemia, arthralgia, myalgia
Ganciclovir
(anti- viral)
Phlebitis, neutropenia, eosinophilia, thrombocytopenia, granulocytopenia, dizziness, headache, arrhythmias, nausea, vomiting, diarrhea
Indinavir
(protease inhibitor)
Isoniazid
(anti- tubercular)
Nephrolithiasis, asymptomatic hyperbilirubinemia, flu- like illness, palpations, anorexia, flatulence, dry mouth, rashes, taste disorder, arthralgias, muscle cramps, decreased mental acuity
(anti- fungal)
Give one hour apart on an empty stomach; indinavir needs acidic environment
Agranulocytosis, hemolytic anemia, aplastic anemia, peripheral neuropathy,
Foods with tyramine
Increased toxicities
Aluminum antacids
Decreased isoniazid absorption
convulsions,
Disulfiram
Psychotic reactions
Carbamazepine, rifampin
Increased risk of hepatotoxicity
Corticosteroids
Decreased therapeutic effectiveness of isoniazid
Isoniazid, rifampin, phenobarbital, amphotericin B, antacids, H2 blockers, didanosine
May decrease absorption and serum level
Phenytoin
Metabolism of both drugs changed
encephalopathy, hepatitis
Itraconazole
Didanosine
Nausea, vomiting, elevated liver function values, hepatitis
JANAC Vol. 7, No. 4, July-August, 1996
Comments
Monitor serum level closely 71
Table 1. Continued Primary Drug/Class
Adverse Effects
Drugs Taken Concurrently
Interactions
Ketoconazole
Nausea, vomiting, diarrhea, headache, pruritus, abdominal pain, hepatitis
Antacids, didanosine, H2 blockers, rifampin, isoniazid
May decrease absorption and serum level
Phenytoin
Metabolism of both drugs changed
Fatigue, diarrhea, insomnia, rash, headache, nausea, abdominal pain, muscle aches, neuropathy, cough, neutropenia, anemia
Trimethoprim / sulfam ethaxozole
Increased serum level
GI irritation, alopecia, thrombophlebitis, carpal tunnel syndrome
None of significance
Sedation, confusion, hypotension, constipation, nausea, vomiting, urine retention, respiratory
Alcohol, CNS depressants, antihistamines
Additive effects
Use together with caution
Ammonium chloride and other urine acidifiers, phenytoin
May reduce methadone effect
Monitor for decreased pain control
Rifampin
Withdrawal symptoms, reduced serum level
Use together cautiously
MAO inhibiters
May result in severe, unpredictable reactions
Reduce initial dose of methadone to 25% of usual dose
Alcohol
Nausea, vomiting, headache, cramps, flushing
Do not use concurrently
Cimetidine
Increased serum level due to decreased clearance
Monitor closely
Disulfiram
Acute psychoses and confusional states
Do not use concurrently
(anti- fungal)
Lamivudine
(anti- retroviral)
Megestrol Acetate
(hormonal agent)
Methadone
(narcotic analgesicagonist)
depression
Metronicazole
(anti- infective)
Nausea, vomiting, anorexia, diarrhea, thrombophlebitis, Candida, headache, dizziness,
Comments
Monitor closely
Ritonavir
Phenobarbital
iii iii ii ill ii ill iil iiiiill iii ii iil ili~il il iii ii iii iii ili iii iil iil ii iii ii iii ill iii iii ilj ii ii ii ili!ii ii iii iill iill ii iljil iil iil iii iii iljiljilji~ iii iii iii ill ji iii iil ii iii ii: iii !il iii:ii;ii:ii ii ili iil ii ii ii iiiii ii iil i~ i//!/~/ 84 )!!
72
Ritonavir contains alcohol, may cause disulfiram- like reactions when given with metronidazole Decreased serum level because of increased hepatic clearance ~!? ! !! !~!i ! !i !! !!!! !!!!! !~!iii iii84!!!! !i ii iii!ii?/?i!il ii!i i!?il 8484iii? d84 ? //U?
JANAC
Monitor closely
~ ~:~;":III~:IIIIILI:II"III I iiiii ilil ii ii fill iiiiill ii~iii ii ii ii iil iil ii
Vo|. 7, No. 4, July-August, 1996
Table 1. Continued Primary Drug/Class
Adverse Effects
Drugs Taken Concrurently
Interactions
Pentamidine (anti- protozoal)
Fever, nausea, diarrhea, headache hypotension,
Zidovudine, antineoplastics, interferon- alpha
Increased risk of bone marrow toxicity
Didanosine, zalcitabine, alcohol
Increased risk of pancreatitis
Eoscarnet, amphotericin B, aminoglycosides, vancomycin
Additive nephrotoxic effects
Alcohol, rifampin, carbamazepine
Decreased serum level
Cimetidine, isoniazid, diazepam, clarithromycin, fluconazole, itraconazole, ketaconazole, metronidazole
Increased serum level due to decreased metabolism
Highly protein bound drugs (trimethoprim/ sulfamethoxazole, aspirin)
Increased risk of toxicity
Zalcitabine
May increase incidence of peripheral neuropathy
Zidovudine
May increase or decrease serum level
Monitor closely
Quinacrine
Potentiates toxicity
Do not use concurrently
rash, vomiting, nephrotoxicity, cardiac arrhythmias, hypoglycemia, neutropenia, hyperglycemia, thrombocytopenia, hypocalcemia, pancreatitis
Phenytoin (anti- convulsant)
Nystagmus, ataxia, diplopia, hypotension, gingival hyperplasia, rashes, hirsutism, nausea thrombocytopenia, leukopenia, agranulocytosis, slurred speech, confusion, vomiting, toxic hepatitis, v. fib, aplastic anemia, exfoliative dermatitis, Stevens-Johnson syndrome
Primaquine (anti- protozoal, anti- malarial)
Epigastric distress, abdominal cramping, acute hemolysis may occur with people who have g6pd deficiency,
Comments
nausea, vomiting, headache, pruritus
Pyrazinamide (anti- tubercular)
Nausea, vomiting, anemia, thrombocytopenia, hyperuricemia, hepatitis
None of significance
Rifabutin (anti- tubercular)
Neutropenia, thrombocytopenia, rash, nausea, vomiting, diarrhea, abdominal pain, headache, myalgia, arthralgia
Ketaconazole
Either serum level may change
Isoniazid
h~creased hepatotoxicity
Monitor both drugs
lndinavir
Increased serum levels
Decrease rifabutin dose by 50%
Ritonavir
Increased serum level
Do not use concurrently
Probenecid
Increased serum level
~ii=iiiiiiilliiiiiliiiiiiiiii~:ill iiiiiiiiiili~iiiiiiilfilliliiiiiiiii~ii ii iil~iiiiiiii iiiiiiiiii~illiliiiiiiiii i ~iiillii ii~iilii ii~ili@i iil iliiil iii~il !iiiili84iii~i!i~iiii~!i i!i!i i!ii~!!i iiilliif!!!il!i~i!!~~!!ii~i!!~i! !~ii!~iii!iiiliililii!:iiiiii~ii~iliii!ii!iliii! iii!ii!ii!! ~i!~i~i!!i~ii!~ii!iiiilil ii illiii84iii~iiii~iil!ii i!iii~!~iii~!!~i~!iili!ii!~ii!!i!iif!i!~i!ii~i!i~ ~!!i~i 84!i~i!i~ii~~i!iiiilliiii~iii iiilii iil i:ili ii!ilii!iiiii!iiiii!!ili~iii!i! i iii~!i ii!~i~i~!!~~!J~!~i!!i~i!!~i!!iii!!~ii~i~i!iii~i!i:iilli!:iili84iliiiil84ii~!:ii84iil i :ii ii ii~i:iii:i:il iii
JANAC Vol.7, No. 4, July-August, 1996
73
Table 1. Continued i!ii~!i!iii!iiiiiiiiiiii~;~i!~i!~i!!i~iiiiii~iiiiliiiill !ii
Primary Drug/Class
Adverse Effects
Drugs Taken Concurrently
Interactions
Rifampin (anti- tubercular)
Hemolytic anemia, nausea, vomiting, drowsiness, abdominal pain, serious hepatotoxicities
Alcohol, isoniazid, ketoconazole, miconazole
Increased risk of hepatotoxicity
Probenecid
Increased serum level
Para- amino salicylate sodium, ketoconazole
Decreased absorption of rifampin
Fluconazole
15% increase in serum level
Ketoconazole
Increased serum level
Rifampin, rifabutin, phenytoin, dexamethazone, carbamezapine
Decreased serum level
Ganciclovir, pentamidine
Similar toxicities, may increase risk of pancreatitis
Ritonavir (protease inhibitor)
Nausea, diarrhea, vomiting, anorexia, abdominal discomfort,
Comments
asthenia, taste perversion, circumoral and peripheral parathesias
Saquinavir (protease inhibitor)
Diarrhea, abdominal discomfort, nausea, mouth sores
Stavudine (anti- retroviral)
Peripheral neuropathy,
Terfenadine (anti- histamine)
Severe cardiac dysfunction
Erythromycin, itraconazole, ketaconazole, fluconazole, clarithromycin, ritonavir, indinavir
May decrease metabolism
Trimethoprimsulfamethoxazole (anti- infective)
Nausea, vomiting, rash, photosensitivity,
Zidovudine, antineoplastics, ganciclovir
Additive bone marrow toxicity
Diuretics
May decrease number of platelets
Problems more common among elderly
Ketoconazole
20% decrease in sulfamethoxazole
No dosage adjustment required
Pyrimethamine
Increased chance of hepatotoxicity
pancreatitis
9 hepatitis, StevensJohnson syndrome, skin reactions, fever, leukopenia, increased liver function tests, photosensitivity
Ritonavir
May cause megaloblastic anemia
May result in lifethreatening arrhythmias; do not use concurrently
Monitor serum iron
~i!84ii!iil ii~!ii!iii!!!iii!~i! ~84~!~!i~84il 84if! ii~iiiiiiiiiii~!Iii!!ii!i!ii!! i!!!! i!ili!i i! ~ili~ii!ili i!iil 84!i 84ii!i! 84!~i84iii~i 84i iii i ill 84184 i!ii!!ii!ii~i!!~7;?~ !84!ilil 84184 ii84i i ~iiiiii!!i~i!iiiii!i!ili!i~ii!i~ i!~!~!!iii!!!iiii!ii?iill iii:iil :ii!ii!i !!ii i!~~ iii!! !!~~iiliii:iliii !ii!~ii ~ ii~!~!!! i!i!i!iii:!i 84iii!:iii!if:!iil !ii 84!i84i~i!i! i!~iilili !iiiii i!i iiiiii!iii~i~i~!~i!84~ii!~i!84!i!ii!iiiiiiiiiiiii ii i !i;ii~i~;i~! ~i!~ii84i ii84184 iil i iii ii iilliiiiI !iili!i i~i ~!iiilli!? iili i i iill!i il !ii j i!i ;!i~ii!~ii!i~~iiiii:iilliili~ii liii i i!ii;i!~i!! i~!!i!ii~illiii fill
74
JANAC Vol.7, No. 4, July-August, 1996
Table 1. Continued Primary Drug/Class
Adverse Effects
Drugs Taken Concurrently
Interactions
Comments
Warfarin (anti- coagulant)
Bleeding, eosinophilia, leukopenia, rash, fever, nausea, vomiting, agranulocytosis
Fluconazole, ciprofloxacin, itraconazole, ketaconazole, aspirin, trimethoprim/sulfamethoxazole, H2 blockers, metronidazole, clarithomycin, isoniazid
May increase prothrombin time thus increase chance of bleeding
Monitor PT
Barbiturates, rifampin, alcohol, oral contraceptives with estrogen
May decrease prothrombin time and decrease anticoagulant effect
Monitor PT
Food in the stomach, antacids, H2 blockers
May decrease serum level
Probenecid, amino glycosides, amphotericin B, foscarnet
May increase serum level thus increasing toxicity level
Ganciclovir, alcohol, pentamidine, zalcitabine
Similar toxicities, increased chance for pancreatitis
Didanosine, stavudine, isoniazid, metronidazole, phenytoin, disulfram, dapsone
Have similar toxicities, may increase chance of neuropathy and/or pancreatitis
Rifabutin, rifampin, clarithromycin
May decrease serum level
Ritonavir
25% decrease in serum level
Trimethoprim / su 1famethoxazole, fluconazole, probenecid
May increase serum level, thus increase toxicity
Trimethoprim/sulfamethoxazole, dapsone, pentamidine, sulfadiazine, pyrimethamine, flucytosine, ganciclovir
Similar toxicities may produce an additive effect
Peripheral neuropathy,
Zalcitabine (anti- retroviral)
pancreatitis, hepatitis, leukopenia, neutropenia, cardiomyopathy, oral ulcers
Headache, abdominal pain, leukopenia,
Zidovudine (anti- retroviral)
seizures, anemia, neutropenia, nausea, vomiting, joint pain
ii ~i!!%1! i~iii:iiiiliiiiiii~iii iiliili ii ~ili
iilii ~ii!ii!i~
~i
iliiiiiii~ii !~!!iii! i!~!~!~ii!!~i!i i!!~i~iii!iillii:iiiliiiii~ii!ii
JANAC Vol.7, No. 4, July-August, 1996
il
ii~iiil ii~~i~ i!~i~i~!~i~i::iii~:iili i~ i !~ i! ~ii~ii ::iiiiii :iil ii ii
No dosage adjustment required
i:iiii ii~il :i~!iiii~i~ii i!!~iif!i!i!ii!iii:iiii ii iilii
!i i!!~i!i: iii
75
Drug Interactions: H o w They Affect Persons Living With HIV/AIDS
an alkaline envirollrnent. While buffers aid in the absorption of didanosine, the nurse must keep in mind that any drug needing an acidic environment for absorption will not be absorbed when given concurrently. Drugs such as dapsone, ketoaconazole, and itraconazole, and members of the f l u o r o q u i n o l o n e f a m i l y (which i n c l u d e s ciprofloxacin) all need an acidic environment for absorption. Giving any of these drugs and didanosine simultaneously may negate the desired therapeutic effect. Nurses administering dapsone and didanosine simultaneously could precipitate a bout of Pneumocystis Carinii Pneumonia because of the lack of adequate prophylaxis. The pH of the gut can be altered by frequent defecation or vomiting. This may be related to a disease process or be the result of an adverse side effect of a medication. Diarrhea is commonly observed in people with AIDS and can be related to the presence of parasites, HIV, Crohn's disease, or malabsorption diseases. HIV medications such as didanosine may initiate or worsen diarrhea, thus changing the pH. One adverse side effect of zidovudine may be severe vomiting, which also may alter the pH. The healthcare provider should not only manage these symptoms, but also be alerted that due to this fluctuation in pH there is a strong possibility that the client is not reaching therapeutic drug levels of oral medications.
Gastrointestinal Motility Disease can alter the motility of the GI tract, thus altering the length of time a drug is available for absorption. Many HIV/AIDS'clients have chronic diarrhea, which, accompanied by an increase in GI tract motility, decreases the a m o u n t of oral m e d i c a t i o n s being absorbed. Drug levels for ~lients having intermittent diarrhea and, therefore, bouts of intermittent increased motility will be even more difficult to assess and control. Motility also can be enhanced or slowed by the administration of certain medications. For example, opiates can decrease motility, increasing the time the primary drug is available in the gut to be absorbed. Drugs such as metoaclopramide can increase motility, causing the opposite effect. 76
Disease States Disease states may alter absorption in several ways. The cells in the lining of the GI tract may be affected in a way that reduces their ability to absorb nutrients, e.g., cell damage from HIV, scarring from herpes simplex virus (HSV) or c y t o m e g a l o v i r u s (CMV) (Sande & Volberding, 1990). Diarrhea, which can have a number of causes including malabsorption syndromes and parasites such as cryptosporidium, decreases the time the drug is available for absorption. Both the ability to swallow (often decreased in cases of esophageal candidiasis) and frequent vomiting may alter the amount of drug administered and time for absorption.
Drug Interactions Drugs also can influence absorption by binding to each other, thus rendering one or both of the drugs inactive. An important instance of two drugs binding occurs when antibiotics belonging to the penicillin or tetracycline families are administered to women who are taking oral contraceptives (Spratto & Woods, 1995). The antibiotic and the contraceptive bind, rendering the contraceptive inactive. As the number of HIV- positive women increases, it will be of growing clinical significance for nurses to know and educate their clients on the interactions between oral contraceptions and other concurrent medications.
Distribution Distribution of medications within the body occurs in stages. During the earliest stages the drug is distributed to high-blood-flow areas of the body. Later, the drug is distributed to the areas having a lower blood flow. The distribution of the drug into the tissue is dependent on this property of blood flow as well as on the proteinbinding properties of the drug and its lipid solubility. Any alteration in these properties will alter the distribution of the drug in the body, which could in turn alter the serum levels (Matthewson-Kuhn, 1994). JANAC Vol.7, No. 4, July-August,1996
Drug Interactions Interactions between drugs can alter the distribution of either one or both of the drugs in several ways. For example, drugs that decrease cardiac output (e.g., calcium channel blockers, beta blockers) will slow hepatic uptake and may cause a rise in serum levels of the primary drug. Also, drugs must be free and not bound to any protein to be active. A drug that changes the protein binding ability of another will change the distribution of the primary drug. Drugs may compete with each other for binding sites in the tissue, which will cause a higher concentration of one or the other of the drugs in the serum. For example, trimethoprim-sulfamethoxazole (bactrim), widely used for the prophylaxis of pneumocystis carinii pneumonia, competes for protein-binding sites when administered concurrently with oral anticoagulants, oral hypoglycemics, phenytoin, salicylates or antiinflammatory agents (Malseed, Goldstein, & Balkon, 1995), resulting in the p o s s i b i l i t y of e l e v a t e d or depressed serum levels of either drug. Even though higher serum levels develop, they may not cause a problem unless a disease state exists that prevents the excess from being excreted from the body, or if the drug has a narrow therapeutic window (e.g., warfarin).
serum level of the coadministered medication. However, there also are a number of drugs that have the opposite effect, causing a decrease in hepatic metabolism of another drug. Among these drugs are cimetidine, disulfiram, clarithromycin, metronidazole, fluconazole, dprofloxacin, and sulfonamides.
Excretion The kidney provides the main route of excretion but drugs also may be excreted through sweat, salivary and mammary glands, the lungs, and intestines. Many drugs have a high clearance rate and are eliminated through the kidneys in their original form. However, many drugs must be transformed (usually by the liver) into more water soluble metabolites before they can be eliminated by the kidneys (Malseed et al., 1995). Conditions that inhibit the actions of either the kidneys or the liver may decrease the amount of drug being excreted, which will increase the amount of drug in the serum or prolong the serum half-life. Due to HIV nephropathy a n d / o r liver impairment, regular monitoring of kidney and liver functioning is needed to provide accurate ilffonnation on which to base dosing regimens.
Age Factors Metabolism The liver metabolizes or biotransforms the majority of drugs; however, the process can occur in the kidneys, lungs, plasma, and intestinal mucosa (MatthewsonKuhn, 1994). If biotransformation is altered in any way, the serum levels of the drugs involved will be changed. Biotransformation refers to the enzymatic alteration of a drug molecule usually in preparation for excretion. Occasionally, the drug becomes active only after this chemical reaction. When drugs are administered concurrently, one drug can increase the rate of hepatic metabolism of another drug. D r u g s from this g r o u p c o m m o n l y u s e d in HIV/AIDS care i n c l u d e dilantin, c a r b a m a z e p i n e , rifampin, and rifabutin. This may lead to an increased JANAC
Vol. 7, No. 4, July-August, 1996
When assessing the rate of excretion, it is important to consider the age of the patient. The very young and the elderly have a reduced capacity to metabolize drugs, which, without a dosage adjustment, may cause elevated serum levels. These two populations also have impaired renal function: newborns because of their imma~xre kidneys, and the elderly because of reduced renal blood flow, decreased glomerular filtration, and a lower rate of chemical secretion (Johnson & Hannah, 1987)
Drug Interactions Excretion through the kidneys may be altered by drug interactions. More of the drug m a y be filtered out because of prior displacement from plasma proteins. 77
D r u g Interactions: H o w T h e y A f f e c t P e r s o n s L i v i n g W i t h H I V / A I D S
Nursing Implications
Drugs also m a y compete for the same transport system, thus inhibiting the excretion of one or both of the drugs.
pH Level Reabsorption in the renal tubule m a y be altered by a change in pH. The excretion of drugs that are weak acids or weak bases m a y be altered by other drugs that affect the p H of the urine (Hansten, 1995). Examples of frequently used drugs include methadone and amphetamines (weak bases) and salicylates (weak acids).
Nephrotoxicity D r u g s also m a y c a u s e n e p h r o t o x i c i t y , w h i c h will r e d u c e the k i d n e y ' s ability to excrete a n o t h e r d r u g . Aminoglycosides, foscarnet, gandclovir, amphotericin B, and pentamidine are all nephrotoxic and close monitoring of concurrently administered drugs primarily eliminated by the kidneys should be practiced.
Pharmacodynamic Properties of Concurrent Dosing W h e n d r u g s h a v i n g similar effects or a d v e r s e side effects are administered, p h a r m a c o d y n a m i c interactions can occur. The effect of the combination m a y be additive, synergistic, or antagonistic. Additive effects occur w h e n two drugs with similar effects are given concurrently and the total effect equals the sum of the two individual effects. A synergistic effect occktrs w h e n two drugs whose effects are not overtly similar are given concurrently, and the total effect is greater than either of the individual effects would be. An antagonistic effect occurs when the total effect of the two drugs is less than either of effects of the individual drugs (Mathewson-Khun, 1994). Drugs m a y be used to elidt a positive additive or synergistic effect, but more often the effect is detrimental to the client's health and occurs without prior planning. Care must be taken to assure that two drugs with similar toxicities are not prescribed concurrentl~ or if there are no other alternatives, that close monitoring is carried out to assess the level of toxidty in a timely manner so that dosage adjustments can be made.
78
As in m a n y other areas of health care, nurses m u s t be c l i e n t a d v o c a t e s w h e n it c o m e s to m e d i c a t i o n s . Medications are crucial to the health and well-being of clients; therefore, it is essential that nurses are knowledgeable about the expected outcomes of taking them. W h e n in doubt, nurses should utilize the services of a p h a r m a c i s t k n o w l e d g e a b l e in the area of H I V / A I D S drugs. As more and more medications are a d d e d to the list of d r u g s b e i n g u s e d for the care of p e o p l e w i t h HIV/AIDS, the n u m b e r of interactions is likely to g r o w a n d m o r e s u r v e i l l a n c e w i l l b e n e e d e d to p r e v e n t unwanted and injurious client outcomes.
References Cheng, B. (1994). Drug interactions. San Francisco: San Francisco Project Inform. Hansten, P. (1995). Mechanisms of drug interactions. In B. Katzung (Ed.), Basic and clinical pharmacoloc,ny (pp. 986- 987). Norwalk, CT: Appleton & Lange. Johnson, G., & Hannah, K. (1987). Pharmacology and the nursing process (2nd ed.). Toronto:Saunders. Lor, E. (1994). Drug-nutrient interactions. San Francisco: San Francisco Project Inform. Malseed, R., Goldstein, E, & Balkon, N. (1995). Pharmacology: Drug ther ~ apy and nursing considen~tions (4th. ed.). Philadelphia: Lippincott. Mathewson-Kuhn, M. (1994). Pharmacotherapeutics: A nursing process approach (3rd ed.). Philadelphia: Davis. Petal, R. (1980). Pharmacoloxy. London: BailliereTendall. Sande, M., & Voberding, P. (1990). The management of AIDS (2nd ed.). Philadelphia: Saunders. Sanford, J. (1992). Drag interactions to watch for during antibiotic therapy. Journal of Critical Illness, 7(3), 450- 459. Spratto, G., & Woods, A. (1995). RN magazine's NDR-95: Nurses drug reference. Albany,NY: Delmar. Torres, G. (1994a). AIDS drug interactions: Part 1. GMHC Treatment Issues, 8(6), 9-12.
JANAC Vol.7, No. 4, July-August,1996
R e f e r e n c e s for Table I
Certification Examination in HIV/AIDS Nursing
Amodio-Groton, M., & Currier, J. (1992). Interactions of HIV drugs. AIDS ClinicalCare, 4(4), 26-29. Baciewicz, A., & Baciewicz, E (1993). Ketoconazole and fluconazole drag interactions.Archiw's of hzternal Medicine, 153, 1970-1976. Balano, K. (1993). Drug-drug interactions betzoeen HIV/AIDS medications. San Francisco:Community Provider AIDSTrainingProject. Deglin, J., & Vallerand,A. (1993). Davis~ drug guide for nurses (3rd ed.). Philadelphia:Davis. Mascolini, M. (1993, November). HIV drug interactions. Positively Aware, 13. Mathewson-Kuhn, M. (1994). Pharmacotherapeutics: A nursing process approach (3rd ed.). Philadelphia: Davis. Paul, S., & Dummer, S. (1992). Topics in clinical pharmacology: Ganciclovir. The American Journal of the Medical Sciences, 304, 272- 276. Skinner, M., & Blaschke, T. (1995). Clinical pharmacokinetics of rifabutin. ClinicalPharmacokinetics,28(2), 115-125. Torres, G. (1994a). AIDS drug interactions: Part I. GMHC Treatment Issues, 8(6), 9 12. Torres, G. (1994b). AIDS drug interactions: Part II. GMHC Treatment Issues, 8(7), 5, 8-9. Wagstaff, A., & Bryson,H. (1994).Foscarnet:A reappraisalof its antiviral activity, pharmacokineticproperties and therapeutic use in innntu'locompromised patients with viral infections.Drugs, 48(2), 199-226. Wilkes, G. (1995). Memory bank for HIV medications. Boston:Jones and Bartlett.
First certification examination October 31, 1996 Cost ANAC member: $200 N o n - A N A C member: $280 The HIV/AIDS Nursing Certification Board (HANCB) is responsible for the development and administration of the Certification Program in HIV/AIDS Nursing. It was established by ANAC to develop and administer the certification examination. Certification is a voluntary process through which the HANCB validates an individual RN's qualifications and knowledge in the specialized area of HIV/AIDS nursing practice. RNs who complete the Certification Examination in HIV/AIDS Nursing will be entitled to indicate board certification status by using the letters ACRN.
Eligibility. Current license as a RN in the United States (or the international equivalent) and at least two years of experience in clinical practice, education, management, or research in HIV/AIDS nursing are recommended for eligibility to take tile Certification Examination in HIV/AIDS Nursing. To obtain the Certification Examination in HIV/AIDS Nursing Handbook for Candidates and application, complete the form below and mail to:
ANAC
HIV/AIDS Nursing Certification Board c / o Professional Testing Corp 1211 Ave. of the Americas/15th floor New York NY 10036
A S S O C I A T I O N OF NURSES IN AIDS CARE
or call/fax: tel: 212/852-0400 fax: 212/852-0414
!G TIONS CHICAGO 1996 O c t o b e r 31-November 3 JANAC Vol. 7, No. 4, July-August, 1996
Name: Address:
city
state
zip
79
Given the diversity and increasing life span of HIV-positive people, medical management of the associated complications is becoming more complex. This complexity is compounded by the growing number of drugs available to treat people with HIV/AIDS. Information regarding the adverse reactions and~or interactions of these drugs in combination is limited. The purpose of this paper is to review what is currently known about synergistic, antagonistic, and potentially toxic interactions. Included is a table containing side effects and interactions among drugs commonly used to treat clients with HIV/AIDS. K e y w o r d s : Drug interaction, HIV/AIDS,
nursing education
JANAC Vol.7, No. 4, July-August,1996
Margaret C. Dykeman, MS, RN, is a Nurse Associate~Nurse Epidemiologist,CookCounty HIV Primary CareCenter, Chicago.Rachael Wallace,RN, is a Nurse Manager, TriadHealth Practice/HIVTreatment Center, Illinois MasonicMedical Center, Chicago.Pamela Ferrell,BSN, RN, is HIV Coordinator, VA Westside Medical Center,Chicago.JohnJasek, BA, is a Data Manager, CookCounty HIV Primary CareCenter, Chicago. Peter V. Tortorice,Pharm D, is an Oncology Clinical Pharmacist,IllinoisMasonic Medical Center, Chicago. T h e complexity of pharmacologically treating a patient with HIV/AIDS is growing, as are the number of new drugs being prescribed. Due to these factors, the potential for drug interactions in this population is increasing rapidly. Sanford (1992) reported that drug interactions occur in 5% of patients taking only a few drugs; however, when clients concurrently receive 10 to 20 drugs, the frequency of interactions may increase to 20%. Drug interactions may be beneficial, but often they are potentially harmful and can contribute to increased morbidity and mortality. Matthewson-Kuhn (1994) states that 5%10% of all admissions to hospitals occur because of adverse drug reactions. HW/AIDS patients, particularly those with advanced disease are especially vulnerable to drug interactions for two reasons. First, people with late stage disease are commonly prescribed more than 10 medications concurrently. Second, many drugs being used are experimental, and little is known about their actions and interactions. Since nurses perform the majority of client teaching, they must continuously update their knowledge concerning the drugs they prescribe or administer to ensure that clients have the best information available on which to base their healthcare derisions. The purpose of this paper is to discuss several reasons why drugs, whether taken alone or in combination with other drugs, may have different effects than expected or desired. Table 1 lists the primary drugs most frequently used in the provision of HIV/AIDS care. Information 67
D r u g Interactions: H o w T h e y A f f e c t P e o p l e L i v i n g W i t h H I V / A I D S
provided in the table includes the drug name and classification; the most frequently noted adverse effects, including both side and toxic effects; and a list of drugs, that may interact with the primary drug when taken concurrently, with specific interactions. Often, management of the interaction is provided. Please note that when the interaction results in an increase or decrease in serum levels, the change refers to the serum level of the primary drug. The table is offered as a quick reference to nurses working in clinical areas and is not meant to be a complete reference. As previously noted, multiple drug therapy is probably the most frequent cause of adverse drug reactions. Penn (1980) defines an adverse drug reaction "as any response to a drug that is noxious and unintended, and which occurs at doses normally used in man" (pp. 3839). The desired therapeutic outcome for most drug therapy depends to a large extent upon reaching and maintaining an optimal level of the drug in the serum. If for some reason the serum level exceeds the optimal range, toxicity may become a problem. If the serum level is below therapeutic range, the patient may not achieve the intended effect of the medication. A number of different factors may alter the serum level of a drug and thus cause unwanted drug reactions. The coadministration of a second medication may lead to a d r u g i n t e r a c t i o n or i n c o m p a t i b i l i t y . Matthewson-Kuhn (1994) makes a distinction between the two. Drug incompatibilities occur when chemical or physical interactions between two drugs change the molecular structure of one or both drugs. A drug interaction alters one or both of the drugs' pharmacological effects due to an interaction between two drugs or drugs and food. The outcomes of incompatibilities and drug interactions are similar, for ~the purpose of this paper, the authors have treated them as being comparable. The interaction between two drugs being administered concurrently may cause increases or decreases in serum levels of one or both of the drugs. Changes in serum levels may be due to one drug altering the absorption, distribution, metabolism, or elimination of the other drug. Drug interactions also may occur because of similar pharmacodynamic properties, including similar toxicities.
68
Absorption Serum levels of drugs administered orally depend largely on how well the drug is absorbed in the gastrointestinal (GI) tract. Absorption along the GI tract can be altered by the ingestion of food, the administration of drugs that change pH levels in the gut or alter GI motility, by disease states, or by drug interaction.
Food Intake There is a clinically significant relationship between food intake and absorption of many of the commonly prescribed medications for people with AIDS. Food enhances the absorption of atovaquone, clofazimine, itraconazole and ketoconazole, which may increase the serum drug level. The absorption of azithromycin, didanosine, zalcitabine, zidovudine, ciprofloxacin, rifampin, and isoniazid is hindered by the presence of food in the stomach (Lor, 1994). A clinical example of the importance of managing food intake to enhance drug absorption is the protease inhibitor, saquinavir, which must be given with a large meal that is high in fat content. pH Level Many medications need an acidic environment for absorption. Acidity levels may be altered, either by bouts of vomiting or diarrhea--frequent complaints of many AIDS patients. Food in the gut or the administration of concurrent drugs such as antacids or H2 blockers also can alter the pH (Torres, 1994a). The concurrent administration of an antacid with a drug needing an acidic environment for absorption will s i g n i f i c a n t l y decrease the a m o u n t of d r u g being absorbed and thus decrease the serum level. For example, giving antacids at the same time as zalcitabine decreases the serum level of zalcitabine by 25% (Cheng, 1994). However, not all drugs work best in an acidic environment. For example, didanosine comes prepared with its own buffers because it can be absorbed only in
JANAC Vol.7, No. 4, July-August,1996
Table 1. Common Actions and Interactions of Drugs Used in the Treatment of HIV/AIDS Primary Drug/Class
Adverse Effects
Drugs Taken Concurrently
Interactions
Acyclovir (anti- viral)
Nausea, phlebitis, nephrotoxicity,
Probenecid
Increases serum levels, toxicity
Zidovudine
Increased drowsiness, lethargy
Intrathecal methotrexate
Increased risk of CNS side effects
Headache, malaise, myalgias, thrombophlebitis , nausea, vomiting, fever, chills, hypokalemia, anemia, nephrotoxicity,
Probenecid
May increase serum levels
Pentamidine, antineoplastics, amino glycosides, foscarnet
Increased risk of kidney toxicity
weight loss, hypotension, metabolic acidosis
Zidovudine, ganciclovir
Increased risk of bone marrow toxicity, anemia
Corticosteroids, synthetic penicillins
May increase risk of hypokalemia
Ketaconazole, fluconazole, itraconazole
May interfere with activity
Erythromycin, itraconazole, ketaconazole, fluconazole, clarithromycin, ritonavir, indinavir
May decrease metabolism
May result in lifethreatening arrhythmias; do not use concurrently
Food
May increase serum levels
Recommended to take with food
Highly protein- bound drugs such as aspirin or warfarin
Will compete with other highly proteinbound drugs
Documentation not proven at this time
Drowsiness, ataxia,
Isoniazid
Increased risk of hepatotoxicity, may decrease serum levels
Monitor serum levels
bone marrow depression with anemia, leokopenia, thrombocytopenia, vertigo, rashes, photosensitivity, fever, chills, hepatitis
Clarithromicin
May increase serum levels
Itraconazole, ketoconazole
May alter serum levels
Penicillin, rifampin
Decrease in serum level
Ritonavir
77% increase in serum level
headache, dizziness, seizures, diarrhea, vomiting, renal failure, serum creatine elevation, inflammation
Amphotericin B (anti- fungal)
Astemizole (anti- histamine)
Sedation, dizziness, dry mouth, cardiac dysfunction, headache, increased appetite, nausea, nervousness
Atovaquone (anti- protozoal)
Rash, nausea, diarrhea, headache, fever, insomnia, asthenia, liver dysfunction
Carbamazepine (anti- convulsant)
Clarithromycin (macrolide antibiotic)
Notes:
Headache, diarrhea, nausea, abnormal taste, dyspepsia, leukopenia, elevated prothrombin time
Comments
Monitor serum levels regularly
Italicized adverse effects are commonly observed; effects in bold are potentially life- threatening. Drug information inserts from a variety of pharmaceutical companies were used as additional references for the body of the table.
JANAC Vol.7, No. 4, July-August, 1996
69
Table 1. Continued Primary Drug/Class
Adverse Effects
Drugs Taken Concurrently
Interactions
Comments
Clincamycin (anti- bacterial)
Diarrhea, nausea, vomiting, abdominal pain, tenesmus, maculopapular rash, urticaria, pseudomembranous colitis (rare)
Erythromycin
In vitro antagonism between drugs
Not recommended for concurrent administration
Kaolin- pectin
May decrease absorption
Administer 2 hours apart
Zidovudine
Increased bone marrow toxicity
Administer 2 hours apart
Didanosine
Decreases absorption via increased gastric pH
Dapsone (anti- bacterial)
Acute hemolysis may occur with people who have g6pd deficiency, hemolysis of red blood cells with anemia, exfoliative dermatitis, peripheral neuropathy (rare) nausea, vomiting, abdominal pain, headache, abnormal liver function tests, rash, vertigo, blurred vision, insomnia
Didanosine, zalcitabine Pyrimethamine ( or other folinic acid antagonists)
May increase risk of peripheral neuropathy Increased risk of hemolysis
Rifampin May cause increased clearance / decreased serum level Trimethoprim Increase in serum level
Didanosine (anti- retroviral)
Myalgia, arthritis, insomnia, diarrhea, nausea, vomiting, rash and pruritis, pancreatitis, leukopenia, peripheral neuropathy, headache
Food in the stomach
May decrease absorption
Do not take with food
H2 blockers, antacids
May increase serum level
Ganciclovir, alcohol, pentamidine, zalcitabine
Similar toxicities, increased chance of pancreatitis
Ritonavir
13% decrease in serum level
Zalcitabine, stavudine alcohol, metronidazole, isoniazid, dapsone
Similar toxicities, increased chance of neuropathy
Ethambutol (anti- tubercular)
Retrobulbar neuritis, head'ache, dizziness,
Zalcitabine, stavudine dapsone, isoniazid
Increased risk of neurotoxicity
Fluconazole (anti- fungal)
Nausea, vomiting, peripheral neuropathy, pancreatitis, abdominal pain, dizziness, headache, hepatotoxicity (rare)
Hydrochlorothiazide
May increase serum level
Rifampin
May decrease serum level
70
No dosage adjustment required
JANAC Vol.7, No. 4, July-August, 1996
Table 1. Continued Primary Drug/Class
Adverse Effects
Drugs Taken Concurrently
Interactions
Foscarnet
Renal failure, anemia, fever, diarrhea,
Amphotericin B, aminoglycosides, cyclosporin
Increased risk of nephrotoxicity
Pentamidine
Life threatening hypocalcemia, nephrotoxidty
Zidovudine
Possible increased incidence of anemia
Zalcitabine, stavudine
Increased risk of nephrotoxicity and peripheral neuropathy
Antineoplastic agents, radiation therapy, zidovudine, dapsone, pentamidine, amphotericin B, trimethoprim/sulfam ethoxazole
Increased risk of bone marrow suppression
Nephrotoxic drugs (e.g., aminoglycosides)
Increased serum creatinine
Use concurrently with caution
Ketaconazole
Increased serum level
Consider reducing dose of indinavir to 600 mg three times daily
Rifampin
Decreased serum level
Co- administration not recommended
(anti- viral)
granulocytopenia, leukopenia, bone marrow suppression, headaches, seizures, nausea, vomiting, hypocalcemia, hypomagnesemia, hypokalemia, arthralgia, myalgia
Ganciclovir
(anti- viral)
Phlebitis, neutropenia, eosinophilia, thrombocytopenia, granulocytopenia, dizziness, headache, arrhythmias, nausea, vomiting, diarrhea
Indinavir
(protease inhibitor)
Isoniazid
(anti- tubercular)
Nephrolithiasis, asymptomatic hyperbilirubinemia, flu- like illness, palpations, anorexia, flatulence, dry mouth, rashes, taste disorder, arthralgias, muscle cramps, decreased mental acuity
(anti- fungal)
Give one hour apart on an empty stomach; indinavir needs acidic environment
Agranulocytosis, hemolytic anemia, aplastic anemia, peripheral neuropathy,
Foods with tyramine
Increased toxicities
Aluminum antacids
Decreased isoniazid absorption
convulsions,
Disulfiram
Psychotic reactions
Carbamazepine, rifampin
Increased risk of hepatotoxicity
Corticosteroids
Decreased therapeutic effectiveness of isoniazid
Isoniazid, rifampin, phenobarbital, amphotericin B, antacids, H2 blockers, didanosine
May decrease absorption and serum level
Phenytoin
Metabolism of both drugs changed
encephalopathy, hepatitis
Itraconazole
Didanosine
Nausea, vomiting, elevated liver function values, hepatitis
JANAC Vol. 7, No. 4, July-August, 1996
Comments
Monitor serum level closely 71
Table 1. Continued Primary Drug/Class
Adverse Effects
Drugs Taken Concurrently
Interactions
Ketoconazole
Nausea, vomiting, diarrhea, headache, pruritus, abdominal pain, hepatitis
Antacids, didanosine, H2 blockers, rifampin, isoniazid
May decrease absorption and serum level
Phenytoin
Metabolism of both drugs changed
Fatigue, diarrhea, insomnia, rash, headache, nausea, abdominal pain, muscle aches, neuropathy, cough, neutropenia, anemia
Trimethoprim / sulfam ethaxozole
Increased serum level
GI irritation, alopecia, thrombophlebitis, carpal tunnel syndrome
None of significance
Sedation, confusion, hypotension, constipation, nausea, vomiting, urine retention, respiratory
Alcohol, CNS depressants, antihistamines
Additive effects
Use together with caution
Ammonium chloride and other urine acidifiers, phenytoin
May reduce methadone effect
Monitor for decreased pain control
Rifampin
Withdrawal symptoms, reduced serum level
Use together cautiously
MAO inhibiters
May result in severe, unpredictable reactions
Reduce initial dose of methadone to 25% of usual dose
Alcohol
Nausea, vomiting, headache, cramps, flushing
Do not use concurrently
Cimetidine
Increased serum level due to decreased clearance
Monitor closely
Disulfiram
Acute psychoses and confusional states
Do not use concurrently
(anti- fungal)
Lamivudine
(anti- retroviral)
Megestrol Acetate
(hormonal agent)
Methadone
(narcotic analgesicagonist)
depression
Metronicazole
(anti- infective)
Nausea, vomiting, anorexia, diarrhea, thrombophlebitis, Candida, headache, dizziness,
Comments
Monitor closely
Ritonavir
Phenobarbital
iii iii ii ill ii ill iil iiiiill iii ii iil ili~il il iii ii iii iii ili iii iil iil ii iii ii iii ill iii iii ilj ii ii ii ili!ii ii iii iill iill ii iljil iil iil iii iii iljiljilji~ iii iii iii ill ji iii iil ii iii ii: iii !il iii:ii;ii:ii ii ili iil ii ii ii iiiii ii iil i~ i//!/~/ 84 )!!
72
Ritonavir contains alcohol, may cause disulfiram- like reactions when given with metronidazole Decreased serum level because of increased hepatic clearance ~!? ! !! !~!i ! !i !! !!!! !!!!! !~!iii iii84!!!! !i ii iii!ii?/?i!il ii!i i!?il 8484iii? d84 ? //U?
JANAC
Monitor closely
~ ~:~;":III~:IIIIILI:II"III I iiiii ilil ii ii fill iiiiill ii~iii ii ii ii iil iil ii
Vo|. 7, No. 4, July-August, 1996
Table 1. Continued Primary Drug/Class
Adverse Effects
Drugs Taken Concrurently
Interactions
Pentamidine (anti- protozoal)
Fever, nausea, diarrhea, headache hypotension,
Zidovudine, antineoplastics, interferon- alpha
Increased risk of bone marrow toxicity
Didanosine, zalcitabine, alcohol
Increased risk of pancreatitis
Eoscarnet, amphotericin B, aminoglycosides, vancomycin
Additive nephrotoxic effects
Alcohol, rifampin, carbamazepine
Decreased serum level
Cimetidine, isoniazid, diazepam, clarithromycin, fluconazole, itraconazole, ketaconazole, metronidazole
Increased serum level due to decreased metabolism
Highly protein bound drugs (trimethoprim/ sulfamethoxazole, aspirin)
Increased risk of toxicity
Zalcitabine
May increase incidence of peripheral neuropathy
Zidovudine
May increase or decrease serum level
Monitor closely
Quinacrine
Potentiates toxicity
Do not use concurrently
rash, vomiting, nephrotoxicity, cardiac arrhythmias, hypoglycemia, neutropenia, hyperglycemia, thrombocytopenia, hypocalcemia, pancreatitis
Phenytoin (anti- convulsant)
Nystagmus, ataxia, diplopia, hypotension, gingival hyperplasia, rashes, hirsutism, nausea thrombocytopenia, leukopenia, agranulocytosis, slurred speech, confusion, vomiting, toxic hepatitis, v. fib, aplastic anemia, exfoliative dermatitis, Stevens-Johnson syndrome
Primaquine (anti- protozoal, anti- malarial)
Epigastric distress, abdominal cramping, acute hemolysis may occur with people who have g6pd deficiency,
Comments
nausea, vomiting, headache, pruritus
Pyrazinamide (anti- tubercular)
Nausea, vomiting, anemia, thrombocytopenia, hyperuricemia, hepatitis
None of significance
Rifabutin (anti- tubercular)
Neutropenia, thrombocytopenia, rash, nausea, vomiting, diarrhea, abdominal pain, headache, myalgia, arthralgia
Ketaconazole
Either serum level may change
Isoniazid
h~creased hepatotoxicity
Monitor both drugs
lndinavir
Increased serum levels
Decrease rifabutin dose by 50%
Ritonavir
Increased serum level
Do not use concurrently
Probenecid
Increased serum level
~ii=iiiiiiilliiiiiliiiiiiiiii~:ill iiiiiiiiiili~iiiiiiilfilliliiiiiiiii~ii ii iil~iiiiiiii iiiiiiiiii~illiliiiiiiiii i ~iiillii ii~iilii ii~ili@i iil iliiil iii~il !iiiili84iii~i!i~iiii~!i i!i!i i!ii~!!i iiilliif!!!il!i~i!!~~!!ii~i!!~i! !~ii!~iii!iiiliililii!:iiiiii~ii~iliii!ii!iliii! iii!ii!ii!! ~i!~i~i!!i~ii!~ii!iiiilil ii illiii84iii~iiii~iil!ii i!iii~!~iii~!!~i~!iili!ii!~ii!!i!iif!i!~i!ii~i!i~ ~!!i~i 84!i~i!i~ii~~i!iiiilliiii~iii iiilii iil i:ili ii!ilii!iiiii!iiiii!!ili~iii!i! i iii~!i ii!~i~i~!!~~!J~!~i!!i~i!!~i!!iii!!~ii~i~i!iii~i!i:iilli!:iili84iliiiil84ii~!:ii84iil i :ii ii ii~i:iii:i:il iii
JANAC Vol.7, No. 4, July-August, 1996
73
Table 1. Continued i!ii~!i!iii!iiiiiiiiiiii~;~i!~i!~i!!i~iiiiii~iiiiliiiill !ii
Primary Drug/Class
Adverse Effects
Drugs Taken Concurrently
Interactions
Rifampin (anti- tubercular)
Hemolytic anemia, nausea, vomiting, drowsiness, abdominal pain, serious hepatotoxicities
Alcohol, isoniazid, ketoconazole, miconazole
Increased risk of hepatotoxicity
Probenecid
Increased serum level
Para- amino salicylate sodium, ketoconazole
Decreased absorption of rifampin
Fluconazole
15% increase in serum level
Ketoconazole
Increased serum level
Rifampin, rifabutin, phenytoin, dexamethazone, carbamezapine
Decreased serum level
Ganciclovir, pentamidine
Similar toxicities, may increase risk of pancreatitis
Ritonavir (protease inhibitor)
Nausea, diarrhea, vomiting, anorexia, abdominal discomfort,
Comments
asthenia, taste perversion, circumoral and peripheral parathesias
Saquinavir (protease inhibitor)
Diarrhea, abdominal discomfort, nausea, mouth sores
Stavudine (anti- retroviral)
Peripheral neuropathy,
Terfenadine (anti- histamine)
Severe cardiac dysfunction
Erythromycin, itraconazole, ketaconazole, fluconazole, clarithromycin, ritonavir, indinavir
May decrease metabolism
Trimethoprimsulfamethoxazole (anti- infective)
Nausea, vomiting, rash, photosensitivity,
Zidovudine, antineoplastics, ganciclovir
Additive bone marrow toxicity
Diuretics
May decrease number of platelets
Problems more common among elderly
Ketoconazole
20% decrease in sulfamethoxazole
No dosage adjustment required
Pyrimethamine
Increased chance of hepatotoxicity
pancreatitis
9 hepatitis, StevensJohnson syndrome, skin reactions, fever, leukopenia, increased liver function tests, photosensitivity
Ritonavir
May cause megaloblastic anemia
May result in lifethreatening arrhythmias; do not use concurrently
Monitor serum iron
~i!84ii!iil ii~!ii!iii!!!iii!~i! ~84~!~!i~84il 84if! ii~iiiiiiiiiii~!Iii!!ii!i!ii!! i!!!! i!ili!i i! ~ili~ii!ili i!iil 84!i 84ii!i! 84!~i84iii~i 84i iii i ill 84184 i!ii!!ii!ii~i!!~7;?~ !84!ilil 84184 ii84i i ~iiiiii!!i~i!iiiii!i!ili!i~ii!i~ i!~!~!!iii!!!iiii!ii?iill iii:iil :ii!ii!i !!ii i!~~ iii!! !!~~iiliii:iliii !ii!~ii ~ ii~!~!!! i!i!i!iii:!i 84iii!:iii!if:!iil !ii 84!i84i~i!i! i!~iilili !iiiii i!i iiiiii!iii~i~i~!~i!84~ii!~i!84!i!ii!iiiiiiiiiiiii ii i !i;ii~i~;i~! ~i!~ii84i ii84184 iil i iii ii iilliiiiI !iili!i i~i ~!iiilli!? iili i i iill!i il !ii j i!i ;!i~ii!~ii!i~~iiiii:iilliili~ii liii i i!ii;i!~i!! i~!!i!ii~illiii fill
74
JANAC Vol.7, No. 4, July-August, 1996
Table 1. Continued Primary Drug/Class
Adverse Effects
Drugs Taken Concurrently
Interactions
Comments
Warfarin (anti- coagulant)
Bleeding, eosinophilia, leukopenia, rash, fever, nausea, vomiting, agranulocytosis
Fluconazole, ciprofloxacin, itraconazole, ketaconazole, aspirin, trimethoprim/sulfamethoxazole, H2 blockers, metronidazole, clarithomycin, isoniazid
May increase prothrombin time thus increase chance of bleeding
Monitor PT
Barbiturates, rifampin, alcohol, oral contraceptives with estrogen
May decrease prothrombin time and decrease anticoagulant effect
Monitor PT
Food in the stomach, antacids, H2 blockers
May decrease serum level
Probenecid, amino glycosides, amphotericin B, foscarnet
May increase serum level thus increasing toxicity level
Ganciclovir, alcohol, pentamidine, zalcitabine
Similar toxicities, increased chance for pancreatitis
Didanosine, stavudine, isoniazid, metronidazole, phenytoin, disulfram, dapsone
Have similar toxicities, may increase chance of neuropathy and/or pancreatitis
Rifabutin, rifampin, clarithromycin
May decrease serum level
Ritonavir
25% decrease in serum level
Trimethoprim / su 1famethoxazole, fluconazole, probenecid
May increase serum level, thus increase toxicity
Trimethoprim/sulfamethoxazole, dapsone, pentamidine, sulfadiazine, pyrimethamine, flucytosine, ganciclovir
Similar toxicities may produce an additive effect
Peripheral neuropathy,
Zalcitabine (anti- retroviral)
pancreatitis, hepatitis, leukopenia, neutropenia, cardiomyopathy, oral ulcers
Headache, abdominal pain, leukopenia,
Zidovudine (anti- retroviral)
seizures, anemia, neutropenia, nausea, vomiting, joint pain
ii ~i!!%1! i~iii:iiiiliiiiiii~iii iiliili ii ~ili
iilii ~ii!ii!i~
~i
iliiiiiii~ii !~!!iii! i!~!~!~ii!!~i!i i!!~i~iii!iillii:iiiliiiii~ii!ii
JANAC Vol.7, No. 4, July-August, 1996
il
ii~iiil ii~~i~ i!~i~i~!~i~i::iii~:iili i~ i !~ i! ~ii~ii ::iiiiii :iil ii ii
No dosage adjustment required
i:iiii ii~il :i~!iiii~i~ii i!!~iif!i!i!ii!iii:iiii ii iilii
!i i!!~i!i: iii
75
Drug Interactions: H o w They Affect Persons Living With HIV/AIDS
an alkaline envirollrnent. While buffers aid in the absorption of didanosine, the nurse must keep in mind that any drug needing an acidic environment for absorption will not be absorbed when given concurrently. Drugs such as dapsone, ketoaconazole, and itraconazole, and members of the f l u o r o q u i n o l o n e f a m i l y (which i n c l u d e s ciprofloxacin) all need an acidic environment for absorption. Giving any of these drugs and didanosine simultaneously may negate the desired therapeutic effect. Nurses administering dapsone and didanosine simultaneously could precipitate a bout of Pneumocystis Carinii Pneumonia because of the lack of adequate prophylaxis. The pH of the gut can be altered by frequent defecation or vomiting. This may be related to a disease process or be the result of an adverse side effect of a medication. Diarrhea is commonly observed in people with AIDS and can be related to the presence of parasites, HIV, Crohn's disease, or malabsorption diseases. HIV medications such as didanosine may initiate or worsen diarrhea, thus changing the pH. One adverse side effect of zidovudine may be severe vomiting, which also may alter the pH. The healthcare provider should not only manage these symptoms, but also be alerted that due to this fluctuation in pH there is a strong possibility that the client is not reaching therapeutic drug levels of oral medications.
Gastrointestinal Motility Disease can alter the motility of the GI tract, thus altering the length of time a drug is available for absorption. Many HIV/AIDS'clients have chronic diarrhea, which, accompanied by an increase in GI tract motility, decreases the a m o u n t of oral m e d i c a t i o n s being absorbed. Drug levels for ~lients having intermittent diarrhea and, therefore, bouts of intermittent increased motility will be even more difficult to assess and control. Motility also can be enhanced or slowed by the administration of certain medications. For example, opiates can decrease motility, increasing the time the primary drug is available in the gut to be absorbed. Drugs such as metoaclopramide can increase motility, causing the opposite effect. 76
Disease States Disease states may alter absorption in several ways. The cells in the lining of the GI tract may be affected in a way that reduces their ability to absorb nutrients, e.g., cell damage from HIV, scarring from herpes simplex virus (HSV) or c y t o m e g a l o v i r u s (CMV) (Sande & Volberding, 1990). Diarrhea, which can have a number of causes including malabsorption syndromes and parasites such as cryptosporidium, decreases the time the drug is available for absorption. Both the ability to swallow (often decreased in cases of esophageal candidiasis) and frequent vomiting may alter the amount of drug administered and time for absorption.
Drug Interactions Drugs also can influence absorption by binding to each other, thus rendering one or both of the drugs inactive. An important instance of two drugs binding occurs when antibiotics belonging to the penicillin or tetracycline families are administered to women who are taking oral contraceptives (Spratto & Woods, 1995). The antibiotic and the contraceptive bind, rendering the contraceptive inactive. As the number of HIV- positive women increases, it will be of growing clinical significance for nurses to know and educate their clients on the interactions between oral contraceptions and other concurrent medications.
Distribution Distribution of medications within the body occurs in stages. During the earliest stages the drug is distributed to high-blood-flow areas of the body. Later, the drug is distributed to the areas having a lower blood flow. The distribution of the drug into the tissue is dependent on this property of blood flow as well as on the proteinbinding properties of the drug and its lipid solubility. Any alteration in these properties will alter the distribution of the drug in the body, which could in turn alter the serum levels (Matthewson-Kuhn, 1994). JANAC Vol.7, No. 4, July-August,1996
Drug Interactions Interactions between drugs can alter the distribution of either one or both of the drugs in several ways. For example, drugs that decrease cardiac output (e.g., calcium channel blockers, beta blockers) will slow hepatic uptake and may cause a rise in serum levels of the primary drug. Also, drugs must be free and not bound to any protein to be active. A drug that changes the protein binding ability of another will change the distribution of the primary drug. Drugs may compete with each other for binding sites in the tissue, which will cause a higher concentration of one or the other of the drugs in the serum. For example, trimethoprim-sulfamethoxazole (bactrim), widely used for the prophylaxis of pneumocystis carinii pneumonia, competes for protein-binding sites when administered concurrently with oral anticoagulants, oral hypoglycemics, phenytoin, salicylates or antiinflammatory agents (Malseed, Goldstein, & Balkon, 1995), resulting in the p o s s i b i l i t y of e l e v a t e d or depressed serum levels of either drug. Even though higher serum levels develop, they may not cause a problem unless a disease state exists that prevents the excess from being excreted from the body, or if the drug has a narrow therapeutic window (e.g., warfarin).
serum level of the coadministered medication. However, there also are a number of drugs that have the opposite effect, causing a decrease in hepatic metabolism of another drug. Among these drugs are cimetidine, disulfiram, clarithromycin, metronidazole, fluconazole, dprofloxacin, and sulfonamides.
Excretion The kidney provides the main route of excretion but drugs also may be excreted through sweat, salivary and mammary glands, the lungs, and intestines. Many drugs have a high clearance rate and are eliminated through the kidneys in their original form. However, many drugs must be transformed (usually by the liver) into more water soluble metabolites before they can be eliminated by the kidneys (Malseed et al., 1995). Conditions that inhibit the actions of either the kidneys or the liver may decrease the amount of drug being excreted, which will increase the amount of drug in the serum or prolong the serum half-life. Due to HIV nephropathy a n d / o r liver impairment, regular monitoring of kidney and liver functioning is needed to provide accurate ilffonnation on which to base dosing regimens.
Age Factors Metabolism The liver metabolizes or biotransforms the majority of drugs; however, the process can occur in the kidneys, lungs, plasma, and intestinal mucosa (MatthewsonKuhn, 1994). If biotransformation is altered in any way, the serum levels of the drugs involved will be changed. Biotransformation refers to the enzymatic alteration of a drug molecule usually in preparation for excretion. Occasionally, the drug becomes active only after this chemical reaction. When drugs are administered concurrently, one drug can increase the rate of hepatic metabolism of another drug. D r u g s from this g r o u p c o m m o n l y u s e d in HIV/AIDS care i n c l u d e dilantin, c a r b a m a z e p i n e , rifampin, and rifabutin. This may lead to an increased JANAC
Vol. 7, No. 4, July-August, 1996
When assessing the rate of excretion, it is important to consider the age of the patient. The very young and the elderly have a reduced capacity to metabolize drugs, which, without a dosage adjustment, may cause elevated serum levels. These two populations also have impaired renal function: newborns because of their imma~xre kidneys, and the elderly because of reduced renal blood flow, decreased glomerular filtration, and a lower rate of chemical secretion (Johnson & Hannah, 1987)
Drug Interactions Excretion through the kidneys may be altered by drug interactions. More of the drug m a y be filtered out because of prior displacement from plasma proteins. 77
D r u g Interactions: H o w T h e y A f f e c t P e r s o n s L i v i n g W i t h H I V / A I D S
Nursing Implications
Drugs also m a y compete for the same transport system, thus inhibiting the excretion of one or both of the drugs.
pH Level Reabsorption in the renal tubule m a y be altered by a change in pH. The excretion of drugs that are weak acids or weak bases m a y be altered by other drugs that affect the p H of the urine (Hansten, 1995). Examples of frequently used drugs include methadone and amphetamines (weak bases) and salicylates (weak acids).
Nephrotoxicity D r u g s also m a y c a u s e n e p h r o t o x i c i t y , w h i c h will r e d u c e the k i d n e y ' s ability to excrete a n o t h e r d r u g . Aminoglycosides, foscarnet, gandclovir, amphotericin B, and pentamidine are all nephrotoxic and close monitoring of concurrently administered drugs primarily eliminated by the kidneys should be practiced.
Pharmacodynamic Properties of Concurrent Dosing W h e n d r u g s h a v i n g similar effects or a d v e r s e side effects are administered, p h a r m a c o d y n a m i c interactions can occur. The effect of the combination m a y be additive, synergistic, or antagonistic. Additive effects occur w h e n two drugs with similar effects are given concurrently and the total effect equals the sum of the two individual effects. A synergistic effect occktrs w h e n two drugs whose effects are not overtly similar are given concurrently, and the total effect is greater than either of the individual effects would be. An antagonistic effect occurs when the total effect of the two drugs is less than either of effects of the individual drugs (Mathewson-Khun, 1994). Drugs m a y be used to elidt a positive additive or synergistic effect, but more often the effect is detrimental to the client's health and occurs without prior planning. Care must be taken to assure that two drugs with similar toxicities are not prescribed concurrentl~ or if there are no other alternatives, that close monitoring is carried out to assess the level of toxidty in a timely manner so that dosage adjustments can be made.
78
As in m a n y other areas of health care, nurses m u s t be c l i e n t a d v o c a t e s w h e n it c o m e s to m e d i c a t i o n s . Medications are crucial to the health and well-being of clients; therefore, it is essential that nurses are knowledgeable about the expected outcomes of taking them. W h e n in doubt, nurses should utilize the services of a p h a r m a c i s t k n o w l e d g e a b l e in the area of H I V / A I D S drugs. As more and more medications are a d d e d to the list of d r u g s b e i n g u s e d for the care of p e o p l e w i t h HIV/AIDS, the n u m b e r of interactions is likely to g r o w a n d m o r e s u r v e i l l a n c e w i l l b e n e e d e d to p r e v e n t unwanted and injurious client outcomes.
References Cheng, B. (1994). Drug interactions. San Francisco: San Francisco Project Inform. Hansten, P. (1995). Mechanisms of drug interactions. In B. Katzung (Ed.), Basic and clinical pharmacoloc,ny (pp. 986- 987). Norwalk, CT: Appleton & Lange. Johnson, G., & Hannah, K. (1987). Pharmacology and the nursing process (2nd ed.). Toronto:Saunders. Lor, E. (1994). Drug-nutrient interactions. San Francisco: San Francisco Project Inform. Malseed, R., Goldstein, E, & Balkon, N. (1995). Pharmacology: Drug ther ~ apy and nursing considen~tions (4th. ed.). Philadelphia: Lippincott. Mathewson-Kuhn, M. (1994). Pharmacotherapeutics: A nursing process approach (3rd ed.). Philadelphia: Davis. Petal, R. (1980). Pharmacoloxy. London: BailliereTendall. Sande, M., & Voberding, P. (1990). The management of AIDS (2nd ed.). Philadelphia: Saunders. Sanford, J. (1992). Drag interactions to watch for during antibiotic therapy. Journal of Critical Illness, 7(3), 450- 459. Spratto, G., & Woods, A. (1995). RN magazine's NDR-95: Nurses drug reference. Albany,NY: Delmar. Torres, G. (1994a). AIDS drug interactions: Part 1. GMHC Treatment Issues, 8(6), 9-12.
JANAC Vol.7, No. 4, July-August,1996
R e f e r e n c e s for Table I
Certification Examination in HIV/AIDS Nursing
Amodio-Groton, M., & Currier, J. (1992). Interactions of HIV drugs. AIDS ClinicalCare, 4(4), 26-29. Baciewicz, A., & Baciewicz, E (1993). Ketoconazole and fluconazole drag interactions.Archiw's of hzternal Medicine, 153, 1970-1976. Balano, K. (1993). Drug-drug interactions betzoeen HIV/AIDS medications. San Francisco:Community Provider AIDSTrainingProject. Deglin, J., & Vallerand,A. (1993). Davis~ drug guide for nurses (3rd ed.). Philadelphia:Davis. Mascolini, M. (1993, November). HIV drug interactions. Positively Aware, 13. Mathewson-Kuhn, M. (1994). Pharmacotherapeutics: A nursing process approach (3rd ed.). Philadelphia: Davis. Paul, S., & Dummer, S. (1992). Topics in clinical pharmacology: Ganciclovir. The American Journal of the Medical Sciences, 304, 272- 276. Skinner, M., & Blaschke, T. (1995). Clinical pharmacokinetics of rifabutin. ClinicalPharmacokinetics,28(2), 115-125. Torres, G. (1994a). AIDS drug interactions: Part I. GMHC Treatment Issues, 8(6), 9 12. Torres, G. (1994b). AIDS drug interactions: Part II. GMHC Treatment Issues, 8(7), 5, 8-9. Wagstaff, A., & Bryson,H. (1994).Foscarnet:A reappraisalof its antiviral activity, pharmacokineticproperties and therapeutic use in innntu'locompromised patients with viral infections.Drugs, 48(2), 199-226. Wilkes, G. (1995). Memory bank for HIV medications. Boston:Jones and Bartlett.
First certification examination October 31, 1996 Cost ANAC member: $200 N o n - A N A C member: $280 The HIV/AIDS Nursing Certification Board (HANCB) is responsible for the development and administration of the Certification Program in HIV/AIDS Nursing. It was established by ANAC to develop and administer the certification examination. Certification is a voluntary process through which the HANCB validates an individual RN's qualifications and knowledge in the specialized area of HIV/AIDS nursing practice. RNs who complete the Certification Examination in HIV/AIDS Nursing will be entitled to indicate board certification status by using the letters ACRN.
Eligibility. Current license as a RN in the United States (or the international equivalent) and at least two years of experience in clinical practice, education, management, or research in HIV/AIDS nursing are recommended for eligibility to take tile Certification Examination in HIV/AIDS Nursing. To obtain the Certification Examination in HIV/AIDS Nursing Handbook for Candidates and application, complete the form below and mail to:
ANAC
HIV/AIDS Nursing Certification Board c / o Professional Testing Corp 1211 Ave. of the Americas/15th floor New York NY 10036
A S S O C I A T I O N OF NURSES IN AIDS CARE
or call/fax: tel: 212/852-0400 fax: 212/852-0414
!G TIONS CHICAGO 1996 O c t o b e r 31-November 3 JANAC Vol. 7, No. 4, July-August, 1996
Name: Address:
city
state
zip
79