Agenerase Side Effects

Please note - some side effects for Agenerase may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

Side Effects of Agenerase - for the Consumer

Agenerase

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome when using Agenerase:

Diarrhea/loose stools; headache; nausea; numbness or tingling around the mouth and in the hands and feet; rash; shift of body fat to stomach and upper back; stomach pain; taste disorders; vomiting.

Seek medical attention right away if any of these SEVERE side effects occur when using Agenerase:

Severe allergic reactions (rash; hives; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); change in mood, emotions, or behavior; clumsiness; depression; excessive urination, thirst, or hunger; fever, chills, or sore throat; muscle pain or stiffness; red, swollen, or blistered skin; seizures; unusual tiredness or weakness; yellowing of the skin or eyes.

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.

Agenerase Solution

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome when using Agenerase Solution:

Diarrhea/loose stools; headache; nausea; numbness or tingling around the mouth and in the hands and feet; rash; shift of body fat to stomach and upper back; stomach pain; taste disorders; vomiting.

Seek medical attention right away if any of these SEVERE side effects occur when using Agenerase Solution:

Severe allergic reactions (rash; hives; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); change in mood, emotions, or behavior; clumsiness; depression; excessive thirst or hunger; fast heartbeat; fast, shallow breathing; fever, chills, or sore throat; increased or decreased urination; muscle pain or cramping; muscle stiffness; red, swollen, or blistered skin; seizures; severe muscle pain or cramping; stomach discomfort; unusual tiredness or weakness; yellowing of the skin or eyes.

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.

Top

Agenerase Side Effects - for the Professional

Agenerase

In clinical studies, adverse events leading to amprenavir discontinuation occurred primarily during the first 12 weeks of therapy, and were mostly due to gastrointestinal events (nausea, vomiting, diarrhea, and abdominal pain/discomfort), which were mild to moderate in severity.

Skin rash occurred in 22% of patients treated with amprenavir in studies PROAB3001 and PROAB3006. Rashes were usually maculopapular and of mild or moderate intensity, some with pruritus. Rashes had a median onset of 11 days after amprenavir initiation and a median duration of 10 days. Skin rashes led to amprenavir discontinuation in approximately 3% of patients. In some patients with mild or moderate rash, amprenavir dosing was often continued without interruption; if interrupted, reintroduction of amprenavir generally did not result in rash recurrence.

Severe or life-threatening rash (Grade 3 or 4), including cases of Stevens-Johnson syndrome, occurred in approximately 1% of recipients of Agenerase. Amprenavir therapy should be discontinued for severe or life-threatening rashes and for moderate rashes accompanied by systemic symptoms.

Table 9. Selected Clinical Adverse Events of All Grades Reported in >5% of Adult Patients

Adverse Event	PROAB3001 Therapy-Naive Patients		PROAB3006 NRTI-Experienced Patients
	Agenerase/Lamivudine/ Zidovudine (n = 113)	Lamivudine/ Zidovudine (n = 109)	Agenerase/NRTI (n = 245)	Indinavir/ NRTI (n = 241)
Digestive
Nausea	74%	50%	43%	35%
Vomiting	34%	17%	24%	20%
Diarrhea or loose stools	39%	35%	60%	41%
Taste disorders	10%	6%	2%	8%
Skin
Rash	27%	6%	20%	15%
Nervous
Paresthesia, oral/perioral	26%	6%	31%	2%
Paresthesia, peripheral	10%	4%	14%	10%
Psychiatric
Depressive or mood disorders	16%	4%	9%	13%

Among amprenavir-treated patients in Phase 3 studies, 2 patients developed de novo diabetes mellitus, 1 patient developed a dorsocervical fat enlargement (buffalo hump), and 9 patients developed fat redistribution.

In studies PROAB3001 and PROAB3006, no increased frequency of Grade 3 or 4 AST, ALT, amylase, or bilirubin elevations was seen compared to controls.

Pediatric Patients

An adverse event profile similar to that seen in adults was seen in pediatric patients.

Concomitant Therapy with Ritonavir

Tables 10 and 11 present adverse clinical events and laboratory abnormalities observed in subjects who received Agenerase plus ritonavir. Since the trials were small, open-label, of varying duration, and often included different patient populations, direct comparisons to the frequency of events with Agenerase alone cannot be made.

Table 10. Selected Clinical Adverse Events of All Grades Reported in Adult Patients in Open-Label Clinical Trials of Agenerase in Combination With Ritonavir

Adverse Event	Agenerase 1,200 mg plus Ritonavir 200 mg q.d.* (n = 101)	Agenerase 600 mg plus Ritonavir 100 mg b.i.d.† (n = 239)
Nausea	31%	23%
Diarrhea/loose stools	30%	28%
Headache	16%	12%
Abdominal symptoms	14%	14%
Vomiting	11%	9%
Rash	10%	9%
Paresthesias	9%	11%
Fatigue	7%	14%
Depressive & mood disorders	4%	9%

* Data from 2 open-label studies in treatment-naive patients also receiving abacavir/lamivudine.

†Data from 3 open-label studies in treatment-naive and treatment-experienced patients receiving combination antiretroviral therapy.

Table 11. Grade 3/4 Laboratory Abnormalities Reported in ≥2% of Adult Patients in Open-Label Clinical Trials of Agenerase in Combination With Ritonavir

Laboratory Abnormality (non-fasting specimens)	Agenerase 1,200 mg plus Ritonavir 200 mg q.d.* (n = 101)	Agenerase 600 mg plus Ritonavir 100 mg b.i.d.† (n = 239)
Hypertriglyceridemia (>750 mg/dL)	8%	13%
Hyperglycemia (>251 mg/dL)	2%	3%
AST (>5 x ULN)	3%	5%
ALT (>5 x ULN)	4%	4%
Amylase (>2 x ULN)	4%	3%

* Data from 2 open-label studies in treatment-naive patients also receiving abacavir/lamivudine.

†Data from 3 open-label studies in treatment-naive and treatment-experienced patients receiving combination antiretroviral therapy.

Top

Side Effects by Body System - for Healthcare Professionals

General

Gastrointestinal side effects and skin rashes were the most frequent side effects in clinical trials of amprenavir in combination with other antiretrovirals. Gastrointestinal effects (nausea, vomiting, diarrhea, and abdominal pain) most often resulted in discontinuation of amprenavir during the first 12 weeks of treatment. Skin rashes had a median onset and duration of 11 and 10 days, respectively, and led to discontinuation of amprenavir in 3% of patients.

Gastrointestinal

Gastrointestinal side effects have included nausea (74%), vomiting (34%), and diarrhea or loose stools (39%) in clinical trials when amprenavir was administered with lamivudine and zidovudine in therapy-naive patients. This compares to an incidence of 50%, 17%, and 34%, respectively, when therapy-naive patients were only administered lamivudine and zidovudine. Abdominal symptoms (unspecified, 14%) and anorexia have been reported in patients receiving amprenavir in combination with ritonavir plus other antiretrovirals.

Dermatologic

Rashes were usually maculopapular, mild to moderate in intensity, and some with pruritus. The onset of rash development was approximately 10 days and ranged from 7 to 73 days. Amprenavir was often continued with mild to moderate rash and if discontinued, rash did not recur when the drug was restarted. Amprenavir should be discontinued for severe or life-threatening rashes and for moderate rashes accompanied by systemic symptoms.

Dermatologic side effects have been reported frequently. Skin rash occurred in 28% of HIV-1 infected patients treated with amprenavir in all multidose studies. Severe or life-threatening rash, including Stevens-Johnson syndrome, occurred in 1% of patients.

Metabolic

Metabolic side effects have included hyperglycemia (37%), hypertriglyceridemia (36%), and hypercholesterolemia (4%) in clinical trials when amprenavir was administered with lamivudine and zidovudine in therapy-naive nonfasting patients. This compares to an incidence of 29%, 22% and 3%, respectively, when therapy-naive nonfasting patients were only administered lamivudine and zidovudine. Grade 3/4 hypertriglyceridemia (8% to 13%) and hyperglycemia (2% to 3%) have been reported in patients receiving amprenavir in combination with ritonavir. New onset and exacerbation of preexisting diabetes mellitus, elevated serum creatine kinase, and ketoacidosis have also been reported.

Hepatic

Hepatic side effects have included elevations in AST (greater than 5 times ULN), ALT (greater than 5 times ULN), and amylase (greater than 2 times ULN) in 3% to 5% of patients receiving amprenavir in combination with ritonavir.

Nervous system

Nervous system side effects have included oral/perioral paresthesia (26%) and other paresthesias (10%), including peripheral paresthesias, in clinical trials when amprenavir was administered with lamivudine and zidovudine in therapy-naive patients. This compares to an incidence of 6% and 4%, respectively, when therapy-naive patients were only administered lamivudine and zidovudine. Headache (12% to 16%) has been reported in patients receiving amprenavir in combination with ritonavir plus other antiretrovirals.

Psychiatric

Psychiatric side effects have included depression and mood disorder in 15% of therapy-naive patients who were administered amprenavir with lamivudine and zidovudine in clinical trials. This compares to an incidence of 4% when therapy-naive patients were only administered lamivudine and zidovudine.

Hematologic

Hematologic side effects have included neutropenia and hemolytic anemia. Hematologic side effects associated with protease inhibitors have included spontaneous bleeding in patients with hemophilia A and B. In many of the reported cases, treatment with protease inhibitors was continued or restarted and some patients required additional factor VIII. A causal relationship between protease inhibitor therapy and these episodes has not been established.

Other

Redistribution/accumulation of body fat, including central obesity, dorsocervical fat enlargement, peripheral wasting, breast enlargement, and "cushingoid appearance" have been observed in patients receiving protease inhibitors. The mechanism and long-term consequences of these events are currently unknown and a causal relationship has not been established. In one case, reduction of neck fat disposition (buffalo hump) was reported when amprenavir replaced indinavir in a regimen.

Other

Other side effects have included taste disorders in 10% of therapy-naive patients who were administered amprenavir with lamivudine and zidovudine in clinical trials. This compares to an incidence of 5% when therapy-naive patients were only administered lamivudine and zidovudine. Fatigue (7% to 14%) and chills have been reported in patients receiving amprenavir in combination with ritonavir plus other antiretrovirals.

Hypersensitivity

Hypersensitivity side effects have included urticaria.

Top

Disclaimer: Every effort has been made to ensure that the information provided is accurate, up-to-date, and complete, but no guarantee is made to that effect. In addition, the drug information contained herein may be time sensitive and should not be utilized as a reference resource beyond the date hereof. This information does not endorse drugs, diagnose patients, or recommend therapy. This drug information is a reference resource designed as supplement to, and not a substitute for, the expertise, skill , knowledge, and judgement of healthcare practitioners in patient care. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug of drug combination is safe, effective, or appropriate for any given patient. Drugs.com does not assume any responsibility for any aspect of healthcare administered with the aid of information provided. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse, or pharmacist.