Currently, there are three classes of drugs used in the management of HIV infected patients. Nucleoside Reverse Transcriptase Inhibitors (NRTIs) include Abacavir, Didanosine, Lamivudine, Stavudine, Zalcitabine and Zidovudine.
The Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) include Efavirenz, Nevirapine, and Delarvidine.
Protease Inhibitors including Saquinavir, Ritonavir, Indinavir, Amprenavir, Nelfinavir, and a combination of Lopinavir and Ritonavir.
Patients who have been offered antiretroviral treatment should be managed with a maximally suppressive regimen (e.g. two NNRTIs and a PI). Clinical issues such as drug toxicity, ability to adhere to treatment regimens, drug interactions and laboratory abnormalities should be considered when initiating therapy and during treatment.
As most patients will be multiple drug therapy, the clinician should be alert to the potential for multiple drug interactions. Thus, the choice of which antiretroviral agent to use must be made with consideration given to potential drug interactions and overlapping drug toxicities.
Other issues to be considered are factors such as wasting and anorexia which may prevent patients from adhering to dietary requirements for efficient absorption of certain protease inhibitors. Bone marrow suppression associated with AZT and the neuropathic effects of ddC, d4T, and ddl may combine with the direct effects of HIV to render the drugs intolerable.
Hepatotoxicity associated with certain Pis may limit the use of these drugs, especially in patients who have underlying liver dysfunction. The absorption and half-life of certain drugs may be altered by anti retrovirals, particularly the Pis and NNRTIs whose metabolism involves the hepatic cytochrome P 450 (CYP450) enzyme pathway. Some of these Pis and NNRTIs (i.e. Ritonavir, Indinavir, Nelfinavir, and Delarvidine) inhibit the CYP450 pathway; others (e.g. Nevirapine) induce the CYP450 metabolism. CYP450 inhibitors have the potential to increase blood levels of drugs metabolized by this pathway.
Adding a CYP40 inhibitor can sometimes improve the pharmacokinetic profile of selected agents (e.g. adding Ritonavir therapy to the hard-gel formulation of Saquinavir) as well as contribute an additive antiviral effect; however, these interactions can also result in life-threatening drug toxicities. As a result, health-care providers should inform their patients of the need to discuss any new drugs, including over-the counter agents and alternative mediations, that they may consider taking, and careful attention should be given to the relative risk versus benefits of specific combinations of agents.
I. Characteristics
Nucleoside Reverse Transcriptase Inhibitors (NRTIs)
Nucleoside analogues |
Dose |
Frequency |
Dietary restrictions |
Major side effects |
Lab monitoring |
Combivir (Lamivudine 150mg, Zidovudine 300mg) tablets (A) |
1 tablet |
BD |
|
Same as Lamivudine and Zidovudine |
Liver function tests. |
Stavudine, d4T, Zerit 30mg & 40mg capsules (A) |
40mg for patients over 60kg; 30mg for patients under 60kg. |
BD |
Take without regard to meals |
Pancreatitis. Peripheral neuropathy. Lactic acidosis with hepatic steatosis is a rare but potentially life-threatening toxicity with use of NRTIs. |
Liver function tests. Renal function tests Complete blood count. |
Zalcitabine, ddC, Hivid 0.75mg tablets (A) 0.375mg (NA) |
0.75mg |
TDS |
Do not take magnesium/ aluminum containing snack. Take without regard to meals. |
Peripheral neuropath. Stomatitis. Lactic acidosis with hepatic steatosis is a rare but potentially life-threatening toxicity with NRTIs. |
Liver function tests. Complete blood count. Serum amylase levels for individuals at risk for pancreatitis. |
Zidovudine, ZDV, AZT, Retrovir 100mg capsules (A) 300mg (NA) |
200mg |
TDS
BD
|
Take without regard to meals |
Bone marrow suppression: Anemia and/or Neutropenia. Subjective complaints: GI intolerance, headache, insomnia, asthenia. Lactic acidosis with hepatic steatosis is a rare but potentially life threatening toxicity with the use of NRTIs |
Liver function tests. Complete blood count with differentials. (RBC indices and Patelet count. |
Abacavir, ABC, Ziagen 300mg tablets (A) |
300mg |
BD |
Take without regard to meals. Alcohol increases ABC levels to 41 % |
Hypersensitivity reaction (can be fatal); Fever, rash, nausea, vomiting, malaise of fatigue and loss of appetite. Respiratory symptoms may also be component (sore throat, cough, SOB) Lactic acidosis with hepatic steatosis-rare. |
Liver function tests. Complete blood count. Routine serum chemistry. |
Didanosine, ddl, Videx 25 & 100mg tablets (A) 50, 150 and 200mg tablets |
>60mg-200mg
<60mg 125mg
|
BD
BD
|
Take 30 min before or 2 hours after food. |
Pancreatitis. Peripheral neuropathy. Nausea. Diarrhea Lactic acidosis with hepatic steatosis is a rare but potentially life threatening toxicity with the use of NRTIs. |
Liver function tests. Complete blood count. Serum amylase. |
Lamivudine, 3TC, Epivir 150mg tablets (A) |
150mg |
BD |
Take without regard to meals. Should not be prescribed to patients requiring dose adjustment |
Pancreatitis Liver disease/hepatitis, severe hepatomegally, steatosis, lactic acidosis. Rash. |
Liver function tests. Renal function tests Complete blood count. |
2) Protease Inhibitors (PIs)
Protease Inhibitor |
Dose |
Frequency |
Lab Monitoring |
Dietary restrictions |
Major side effects |
Nelfinavir, Viracept 250mg tablets (A) |
750mg or 1250mg |
TDS
BD
|
Routine clinical chemistry including HB, neutropil and lymphocyte counts as well as ALT, AST and CK monitoring |
Take with meal or snack |
Diarrhea. Hyperglycemia Fat redistribution and lipid abnormalities. Possible increased bleeding episodes in patients with hemophilia |
Indinavir Crixivan 400mg capsules (A) 200mg capsules (NA) |
800mg |
TDS |
Liver function tests. Renal function tests. Complete blood count with differentials and routine blood chemistry every 2-4 weeks. or low fat meal. |
To be taken on an empty stomach 1 hour before of 2 hours after meal. Plenty of fluids to be taken approx. 1.5 L per day. May take with skim milk increased bleeding episodes in patients with hemophilia. |
Nephrolithiasis. GI intolerance, nausea. Misc.: headache, asthenia, blurred vision, Dizziness, rash, metallic taste, thrombocytopenia, alopecia. Hyperglycemia Fat, redistribution and lipid abnormalities Possible |
Ritonavir Norvir 100mg capsules (A) |
600mg |
BD
NB. Dose escalation required for Ritonavir to improve tolerability Day 1-2: 300mg BD; Day 3-5: 400mg BD; Day 6-13 500mg BD; Day 14-: 600mg BD. |
Complete blood count Routine blood chemistry. Liver function tests and serum lipid/lipoprotein profile every 2-4 weeks. |
Should be refrigerated. Take with meals. This may improve tolerability |
GI intolerance, nausea, vomiting, diarrhea. Parenthesis- circumpolar and extremities. Hepatitis Pancreatitis Asthenia Taste perversion Hyperglycemia Fat redistribution and lipid abnormalities Possible increased bleeding episodes in patients with hemophilia. |
Saquinavir (hard gel) formulation Invirase 200mg capsules (A) |
600mg |
TDS |
Complete blood count and routine blood chemistry periodically. |
Take within 2 hours of a meal. Oral bioavailability is erratic. |
GI intolerance, nausea and diarrhea. Headache. Hyperglycemia Fat redistribution and lipid abnormalities Possible increase bleeding episodes with hemophilia. |
Saquinavir (soft gel) formulation Fortovase 200mg capsules |
1200mg |
TDS |
Complete blood count and routine blood chemistry periodically. |
Take with large meal. This increase levels 6-fold |
GI intolerance, nausea, diarrhea, abdominal pain and dyspepsia. Headache, Hyperglycemia Fat redistribution and lipid abnormalities. Possible increased bleeding episodes in patient with hemophilia. |
Amprenavir Agenerase 50, 100mg capsules 15mg.ml oral solution. NB. Capsules and solution not interchangeable on mg per mg basis. (NA) |
>50kg: 1200mg BID capsules 1400mg BID oral solution
<50kg: 20mg/kg BD capsules Maximum 2400mg/day
>50kg: 1.5ml/kg BID oral solution maximum 2800mg/day |
BID |
Hepatic renal/function. Routine blood chemistry. |
With or without meals but not with a high fat meal since this decreased bioavailability. |
GI intolerance, nausea vomiting, diarrhea Rash parenthesis Fat redistribution and lipid abnormalities Hyperglycemia Possible increased bleeding episodes in patients with hemophilia. |
Lopinavir + Ritonavir Kaletra-133.3mg Lopinavir 4-33.3 mg Ritonavir (capsules). (NA) |
400mg Lopinavir + 100mg Ritonavir. |
BID |
As for Ritonavir |
To be taken with food: moderate fat meal increased bioavailability. |
|
3) Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)
Drug (NNRTI) |
Dose |
Frequency |
Lab Monitoring |
Dietary restrictions |
Major side effects |
Efavirenz Stocrin 200mg capsules - (A) 50, 100mg capsules- (NA) |
600mg |
OD |
Routine blood chemistry. Liver function tests. Cholesterol levels. |
High fat meals should be avoided |
Rash. Central nervous system symptoms |
Nevirapine Viramune 200mg capsules - (A) |
200mg. Dose escalation required to improve tolerability: 200mg OD for 14 days: then 200mg BD from day 15 onwards |
BD |
Liver function tests Renal function tests Routine blood chemistry and complete blood count periodically during therapy. |
Take without regard to meals |
Rash
Hepatitis |
Delarvidine Rescriptor 100, 200mg tablets (NA) |
400mg |
TDS |
Liver function tests Renal function tests. Routine blood chemistry and complete blood count periodically during therapy. |
Take without regard to meals: separate dosing with ddl or antacids by 1 hour. |
Rash (usually mild)
Headache
Nausea
Vomiting |
