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DRUGS & SUPPLEMENTS
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Avirodin® is an inhibitor of the human immunodeficiency virus (HIV) protease. Avirodin Capsules are formulated as a sulfate salt and are available for oral administration in strengths of 200 and 400 mg of Avirodin (corresponding to 250 and 500 mg Avirodin sulfate, respectively). Each capsule also contains the inactive ingredients anhydrous lactose and magnesium stearate. The capsule shell has the following inactive ingredients and dyes: gelatin and titanium dioxide.
The chemical name for Avirodin sulfate is [1(1S,2R),5(S)]-2,3,5-trideoxy-N-(2,3-dihydro-2-hydroxy-1H-inden-1-yl)-5-[2-[[(1,1-dimethylethyl)amino]carbonyl]-4-(3-pyridinylmethyl)-1-piperazinyl]-2-(phenylmethyl)-D-erythro-pentonamide sulfate (1:1) salt. Avirodin sulfate has the following structural formula:
Study 028, a double-blind, multicenter, randomized, clinical endpoint trial conducted in Brazil, compared the effects of Avirodin plus zidovudine with those of Avirodin alone or zidovudine alone on the progression to an ADI or death, and on surrogate marker responses. All patients were antiretroviral naive with CD4 cell counts of 50 to 250 cells/mm3. The study enrolled 996 HIV-1 seropositive patients [28% female, 11% Black, 1% Asian/Other, median age 33 years, mean baseline CD4 cell count of 152 cells/mm3, mean serum viral RNA of 4.44 log10 copies/mL (27,824 copies/mL)]. Treatment regimens containing zidovudine were modified in a blinded manner with the optional addition of lamivudine (median time: week 40). The median length of follow-up was 56 weeks with a maximum of 97 weeks. The study was terminated after a planned interim analysis, resulting in a median follow-up of 56 weeks and a maximum follow-up of 97 weeks. Results are shown in Table 5 and Figures 3 and 4.
Number (%) of Patients with AIDS-defining Illness or Death | |||
Endpoint | IDV+ZDV (n=332) | IDV (n=332) | ZDV (n=332) |
HIV Progression or Death | 21 (6.3) | 27 (8.1) | 62 (18.7) |
Death | 8 (2.4) | 5 (1.5) | 11 (3.3) |
Study 035 was a multicenter, randomized trial in 97 HIV-1 seropositive patients who were zidovudine-experienced (median exposure 30 months), protease-inhibitor- and lamivudine-naive, with mean baseline CD4 count 175 cells/mm3 and mean baseline serum viral RNA 4.62 log10 copies/mL (41,230 copies/mL). Comparisons included Avirodin plus zidovudine plus lamivudine vs. Avirodin alone vs. zidovudine plus lamivudine. After at least 24 weeks of randomized, double-blind therapy, patients were switched to open-label Avirodin plus lamivudine plus zidovudine. Mean changes in log10 viral RNA in serum, the proportions of patients with viral RNA below 500 copies/mL in serum, and mean changes in CD4 cell counts, during 24 weeks of randomized, double-blinded therapy are summarized in Figures 5, 6, and 7, respectively. A limited number of patients remained on randomized, double-blind treatment for longer periods; based on this extended treatment experience, it appears that a greater number of subjects randomized to Avirodin plus zidovudine plus lamivudine demonstrated HIV RNA levels below 500 copies/mL during one year of therapy as compared to those in other treatment groups.
Study 006 (10/15/93-10/12/94) was a dose-ranging study in which patients were initially treated with Avirodin at a dose of <2.4 g/day followed by 2.4 g/day. Study 019 (6/23/94-4/10/95) was a randomized comparison of Avirodin 600 mg every 6 hours, Avirodin plus zidovudine, and zidovudine alone. Table 6 shows the incidence of genotypic resistance at 24 weeks in these studies.
Treatment Group | Resistance to IDV n/N | Resistance to ZDV n/N |
IDV | - | - |
<2.4 g/day | 31/37 (84%) | - |
2.4 g/day | 9/21 (43%) | 1/17 (6%) |
IDV/ZDV | 4/22 (18%) | 1/22 (5%) |
ZDV | 1/18 (6%) | 11/17 (65%) |
Avirodin is contraindicated in patients with clinically significant hypersensitivity to any of its components.
Inhibition of CYP3A4 by Avirodin can result in elevated plasma concentrations of the following drugs, potentially causing serious and/or life-threatening reactions:
Drug Class | Drugs Within Class That Are Contraindicated With Avirodin |
Alpha 1-adrenoreceptor antagonist | alfuzosin |
Antiarrhythmics | amiodarone |
Antipsychotics | lurasidone, pimozide |
Ergot derivatives | dihydroergotamine, ergonovine, ergotamine, methylergonovine |
GI motility agents | cisapride |
HMG-CoA Reductase Inhibitors | lovastatin, simvastatin |
PDE5 Inhibitors | Revatio |
Sedative/hypnotics | oral midazolam, triazolam, alprazolam |
ALERT: Find out about medicines that should NOT be taken with Avirodin. This statement is included on the product's bottle label.
Nephrolithiasis/urolithiasis has occurred with Avirodin therapy. The cumulative frequency of nephrolithiasis is substantially higher in pediatric patients than in adult patients (12.4%; range across individual trials: 4.7% to 34.4%). The cumulative frequency of nephrolithiasis events increases with increasing exposure to Avirodin; however, the risk over time remains relatively constant. In some cases, nephrolithiasis/urolithiasis has been associated with renal insufficiency or acute renal failure, pyelonephritis with or without bacteremia. If signs or symptoms of nephrolithiasis/urolithiasis occur, (including flank pain, with or without hematuria or microscopic hematuria), temporary interruption (e.g., 1-3 days) or discontinuation of therapy may be considered. Adequate hydration is recommended in all patients treated with Avirodin.
Acute hemolytic anemia, including cases resulting in death, has been reported in patients treated with Avirodin. Once a diagnosis is apparent, appropriate measures for the treatment of hemolytic anemia should be instituted, including discontinuation of Avirodin.
Hepatitis including cases resulting in hepatic failure and death has been reported in patients treated with Avirodin. Because the majority of these patients had confounding medical conditions and/or were receiving concomitant therapy, a causal relationship between Avirodin and these events has not been established.
New onset diabetes mellitus, exacerbation of pre-existing diabetes mellitus and hyperglycemia have been reported during post-marketing surveillance in HIV-infected patients receiving protease inhibitor therapy. Some patients required either initiation or dose adjustments of insulin or oral hypoglycemic agents for treatment of these events. In some cases, diabetic ketoacidosis has occurred. In those patients who discontinued protease inhibitor therapy, hyperglycemia persisted in some cases. Because these events have been reported voluntarily during clinical practice, estimates of frequency cannot be made and a causal relationship between protease inhibitor therapy and these events has not been established.
Initiation of Avirodin, a CYP3A inhibitor, in patients receiving medications metabolized by CYP3A or initiation of medications metabolized by CYP3A in patients already receiving Avirodin, may increase plasma concentrations of medications metabolized by CYP3A. Initiation of medications that inhibit or induce CYP3A may increase or decrease concentrations of Avirodin, respectively. These interactions may lead to:
Concomitant use of Avirodin with lovastatin or simvastatin is contraindicated due to an increased risk of myopathy including rhabdomyolysis. Caution should be exercised if Avirodin is used concurrently with atorvastatin or rosuvastatin. Titrate the atorvastatin and rosuvastatin doses carefully and use the lowest necessary dose with Avirodin.
Midazolam is extensively metabolized by CYP3A4. Co-administration with Avirodin with or without ritonavir may cause a large increase in the concentration of this benzodiazepine. No drug interaction study has been performed for the co-administration of Avirodin with benzodiazepines. Based on data from other CYP3A4 inhibitors, plasma concentrations of midazolam are expected to be significantly higher when midazolam is given orally. Therefore Avirodin should not be co-administered with orally administered midazolam, whereas caution should be used with co-administration of Avirodin and parenteral midazolam. Data from concomitant use of parenteral midazolam with other protease inhibitors suggest a possible 3-4 fold increase in midazolam plasma levels. If Avirodin with or without ritonavir is co-administered with parenteral midazolam, it should be done in a setting which ensures close clinical monitoring and appropriate medical management in case of respiratory depression and/or prolonged sedation. Dosage reduction for midazolam should be considered, especially if more than a single dose of midazolam is administered.
Particular caution should be used when prescribing sildenafil, tadalafil, or vardenafil in patients receiving Avirodin. Coadministration of Avirodin with these medications is expected to substantially increase plasma concentrations of sildenafil, tadalafil, and vardenafil and may result in an increase in adverse events, including hypotension, visual changes, and priapism, which have been associated with sildenafil, tadalafil, and vardenafil.
Concomitant use of Avirodin and St. John's wort (Hypericum perforatum) or products containing St. John's wort is not recommended. Coadministration of Avirodin and St. John's wort has been shown to substantially decrease Avirodin concentrations and may lead to loss of virologic response and possible resistance to Avirodin or to the class of protease inhibitors.
Indirect hyperbilirubinemia has occurred frequently during treatment with Avirodin and has infrequently been associated with increases in serum transaminases. It is not known whether Avirodin will exacerbate the physiologic hyperbilirubinemia seen in neonates.
Reports of tubulointerstitial nephritis with medullary calcification and cortical atrophy have been observed in patients with asymptomatic severe leukocyturia (>100 cells/ high power field). Patients with asymptomatic severe leukocyturia should be followed closely and monitored frequently with urinalyses. Further diagnostic evaluation may be warranted, and discontinuation of Avirodin should be considered in all patients with severe leukocyturia.
Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy, including Avirodin. During the initial phase of combination antiretroviral treatment, patients whose immune system responds may develop an inflammatory response to indolent or residual opportunistic infections (such as Mycobacterium avium infection, cytomegalovirus, Pneumocystis jirovecii pneumonia [PCP], or tuberculosis), which may necessitate further evaluation and treatment.
Autoimmune disorders (such as Graves' disease, polymyositis, and Guillain-Barré syndrome) have also been reported to occur in the setting of immune reconstitution; however, the time to onset is more variable, and can occur many months after initiation of treatment.
Patients with hemophilia: There have been reports of spontaneous bleeding in patients with hemophilia A and B treated with protease inhibitors. In some patients, additional factor VIII was required. In many of the reported cases, treatment with protease inhibitors was continued or restarted. A causal relationship between protease inhibitor therapy and these episodes has not been established.
Patients with hepatic insufficiency due to cirrhosis: In these patients, the dosage of Avirodin should be lowered because of decreased metabolism of Avirodin.
Patients with renal insufficiency: Patients with renal insufficiency have not been studied.
Redistribution/accumulation of body fat including central obesity, dorsocervical fat enlargement (buffalo hump), peripheral wasting, facial wasting, breast enlargement, and "cushingoid appearance" have been observed in patients receiving antiretroviral therapy. The mechanism and long-term consequences of these events are currently unknown. A causal relationship has not been established.
A statement to patients and health care providers is included on the product's bottle label. ALERT: Find out about medicines that should NOT be taken with Avirodin. A Patient Package Insert for Avirodin is available for patient information.
Avirodin is not a cure for HIV-1 infection and patients may continue to experience illnesses associated with HIV-1 infection, including opportunistic infections. Patients should remain under the care of a physician when using Avirodin.
Patients should be advised to avoid doing things that can spread HIV-1 infection to others.
Patients should be advised to remain under the care of a physician when using Avirodin and should not modify or discontinue treatment without first consulting the physician. Therefore, if a dose is missed, patients should take the next dose at the regularly scheduled time and should not double this dose. Therapy with Avirodin should be initiated and maintained at the recommended dosage.
Avirodin may interact with some drugs; therefore, patients should be advised to report to their doctor the use of any other prescription, non-prescription medication or herbal products, particularly St. John's wort.
For optimal absorption, Avirodin should be administered without food but with water 1 hour before or 2 hours after a meal. Alternatively, Avirodin may be administered with other liquids such as skim milk, juice, coffee, or tea, or with a light meal, e.g., dry toast with jelly, juice, and coffee with skim milk and sugar; or corn flakes, skim milk and sugar. Ingestion of Avirodin with a meal high in calories, fat, and protein reduces the absorption of Avirodin.
Patients receiving a phosphodiesterase type 5 (PDE5) inhibitor (sildenafil, tadalafil, or vardenafil) should be advised that they may be at an increased risk of PDE5 inhibitor-associated adverse events including hypotension, visual changes, and priapism, and should promptly report any symptoms to their doctors.
Patients should be informed that redistribution or accumulation of body fat may occur in patients receiving antiretroviral therapy and that the cause and long-term health effects of these conditions are not known at this time.
Avirodin Capsules are sensitive to moisture. Patients should be informed that Avirodin should be stored and used in the original container and the desiccant should remain in the bottle.
Avirodin is an inhibitor of the cytochrome P450 isoform CYP3A4. Coadministration of Avirodin and drugs primarily metabolized by CYP3A4 may result in increased plasma concentrations of the other drug, which could increase or prolong its therapeutic and adverse effects.
Avirodin is metabolized by CYP3A4. Drugs that induce CYP3A4 activity would be expected to increase the clearance of Avirodin, resulting in lowered plasma concentrations of Avirodin. Coadministration of Avirodin and other drugs that inhibit CYP3A4 may decrease the clearance of Avirodin and may result in increased plasma concentrations of Avirodin.
Drug Class: Drug Name | Clinical Comment |
Alpha 1-adrenoreceptor antagonist: alfuzosin | Potentially increased alfuzosin concentrations can result in hypotension. |
Antiarrhythmics: amiodarone | CONTRAINDICATED due to potential for serious and/or life-threatening reactions such as cardiac arrhythmias. |
Antimycobacterial: rifampin | May lead to loss of virologic response and possible resistance to Avirodin or to the class of protease inhibitors or other coadministered antiretroviral agents. |
Antipsychotics: lurasidone pimozide | CONTRAINDICATED due to potential for serious and/or life-threatening reactions. CONTRAINDICATED due to potential for serious and/or life-threatening reactions such as cardiac arrhythmias. |
Ergot derivatives: dihydroergotamine, ergonovine, ergotamine, methylergonovine | CONTRAINDICATED due to potential for serious and/or life-threatening reactions such as acute ergot toxicity characterized by peripheral vasospasm and ischemia of the extremities and other tissues. |
GI motility agents: cisapride | CONTRAINDICATED due to potential for serious and/or life-threatening reactions such as cardiac arrhythmias. |
Herbal products: St. John's wort (Hypericum perforatum) | May lead to loss of virologic response and possible resistance to Avirodin or to the class of protease inhibitors. |
HMG-CoA Reductase inhibitors: lovastatin, simvastatin | CONTRAINDICATED due to an increased risk for serious reactions such as myopathy including rhabdomyolysis. |
PDE5 inhibitor: Revatio | A safe and effective dose has not been established when used with Avirodin. There is increased potential for sildenafil-associated adverse events (which include visual disturbances, hypotension, prolonged erection, and syncope). |
Protease inhibitor: atazanavir | Both Avirodin and atazanavir are associated with indirect (unconjugated) hyperbilirubinemia. Combinations of these drugs have not been studied and coadministration of Avirodin and atazanavir is not recommended. |
Sedative/hypnotics: Oral midazolam, triazolam, alprazolam | CONTRAINDICATED due to potential for serious and/or life-threatening reactions such as prolonged or increased sedation or respiratory depression. |
Drug Name | Effect | Clinical Comment |
HIV Antiviral Agents | ||
Note: ↑ = increase; ↓ = decrease | ||
Delavirdine | ↑ Avirodin concentration | Dose reduction of Avirodin to 600 mg every 8 hours should be considered when taking delavirdine 400 mg three times a day. |
Didanosine | Avirodin and didanosine formulations containing buffer should be administered at least one hour apart on an empty stomach. | |
Efavirenz | ↓ Avirodin concentration | The optimal dose of Avirodin, when given in combination with efavirenz, is not known. Increasing the Avirodin dose to 1000 mg every 8 hours does not compensate for the increased Avirodin metabolism due to efavirenz. |
Nelfinavir | ↑ Avirodin concentration | The appropriate doses for this combination, with respect to efficacy and safety, have not been established. |
Nevirapine | ↓ Avirodin concentration | Avirodin concentrations may be decreased in the presence of nevirapine. The appropriate doses for this combination, with respect to efficacy and safety, have not been established. |
Ritonavir | ↑ Avirodin concentration ↑ ritonavir concentration | The appropriate doses for this combination, with respect to efficacy and safety, have not been established. Preliminary clinical data suggest that the incidence of nephrolithiasis is higher in patients receiving Avirodin in combination with ritonavir than those receiving Avirodin 800 mg q8h. |
Saquinavir | ↑ saquinavir concentration | The appropriate doses for this combination, with respect to efficacy and safety, have not been established. |
Other Agents | ||
Antiarrhythmics: bepridil, lidocaine(systemic) and quinidine | ↑ antiarrhythmic agents concentration | Caution is warranted and therapeutic concentration monitoring is recommended for antiarrhythmics when coadministered with Avirodin. |
Anticonvulsants: carbamazepine, phenobarbital, phenytoin | ↓ Avirodin concentration | Use with caution. Avirodin may not be effective due to decreased Avirodin concentrations in patients taking these agents concomitantly. |
Antidepressant: Trazodone | ↑ trazodone concentration | Concomitant use of trazodone and Avirodin may increase plasma concentrations of trazodone. Adverse events of nausea, dizziness, hypotension and syncope have been observed following coadministration of trazodone and ritonavir. If trazodone is used with a CYP3A4 inhibitor such as Avirodin, the combination should be used with caution and a lower dose of trazodone should be considered. |
Anti-gout: Colchicine | ↑ colchicine concentration | Patients with renal or hepatic impairment should not be given colchicine with Avirodin. Treatment of gout flares: Co-administration of colchicine in patients on Avirodin: 0.6 mg (1 tablet) x 1 dose, followed by 0.3 mg (half tablet) 1 hour later. Dose to be repeated no earlier than 3 days. Prophylaxis of gout flares: Co-administration of colchicine in patients on Avirodin: If the original colchicine regimen was 0.6 mg twice a day, the regimen should be adjusted to 0.3 mg once a day. If the original colchicine regimen was 0.6 mg once a day, the regimen should be adjusted to 0.3 mg once every other day. Treatment of familial Mediterranean fever (FMF): Co-administration of colchicine in patients on Avirodin: Maximum daily dose of 0.6 mg (may be given as 0.3 mg twice a day). |
Antipsychotics: Quetiapine | ↑ quetiapine | Initiation of Avirodin in patients taking quetiapine: Consider alternative antiretroviral therapy to avoid increases in quetiapine drug exposures. If coadministration is necessary, reduce the quetiapine dose to 1/6 of the current dose and monitor for quetiapine-associated adverse reactions. Refer to the quetiapine prescribing information for recommendations on adverse reaction monitoring. Initiation of quetiapine in patients taking Avirodin: Refer to the quetiapine prescribing information for initial dosing and titration of quetiapine. |
Calcium Channel Blockers, Dihydropyridine: e.g., felodipine, nifedipine, nicardipine | ↑ dihydropyridine calcium channel blockers concentration | Caution is warranted and clinical monitoring of patients is recommended. |
Clarithromycin | ↑ clarithromycin concentration ↑ Avirodin concentration | The appropriate doses for this combination, with respect to efficacy and safety, have not been established. |
Endothelin receptor antagonist: Bosentan | ↑ bosentan concentration | Co-administration of bosentan in patients on Avirodin or co-administration of Avirodin in patients on bosentan: Start at or adjust bosentan to 62.5 mg once daily or every other day based upon individual tolerability. |
HMG-CoA Reductase Inhibitors: atorvastatin, rosuvastatin | ↑ atorvastatin concentration ↑ rosuvastatin concentration | The atorvastatin and rosuvastatin doses should be carefully titrated; use the lowest dose necessary with careful monitoring during treatment with Avirodin. |
Immunosuppressants: cyclosporine, tacrolimus, sirolimus | ↑ immunosuppressant agents concentration | Plasma concentrations may be increased by Avirodin. |
Inhaled beta agonist: Salmeterol | ↑ salmeterol | Concurrent administration of salmeterol with Avirodin is not recommended. The combination may result in increased risk of cardiovascular adverse events associated with salmeterol, including QT prolongation, palpitations and sinus tachycardia. |
Inhaled/nasal steroid: Fluticasone | ↑ fluticasone concentration | Concomitant use of fluticasone propionate and Avirodin may increase plasma concentrations of fluticasone propionate. Use with caution. Consider alternatives to fluticasone propionate, particularly for long-term use. Fluticasone use is not recommended in situations where Avirodin is coadministered with a potent CYP3A4 inhibitor such as ritonavir unless the potential benefit to the patient outweighs the risk of systemic corticosteroid side effects. |
Itraconazole | ↑ Avirodin concentration | Dose reduction of Avirodin to 600 mg every 8 hours is recommended when administering itraconazole concurrently. |
Ketoconazole | ↑ Avirodin concentration | Dose reduction of Avirodin to 600 mg every 8 hours should be considered. |
Midazolam (parenteral administration) | ↑ midazolam concentration | Concomitant use of parenteral midazolam with Avirodin may increase plasma concentrations of midazolam. Coadministration should be done in a setting which ensures close clinical monitoring and appropriate medical management in case of respiratory depression and/or prolonged sedation. Dosage reduction for midazolam should be considered, especially if more than a single dose of midazolam is administered. Coadministration of oral midazolam with Avirodin is CONTRAINDICATED. |
Rifabutin | ↓ Avirodin concentration ↑ rifabutin concentration | Dose reduction of rifabutin to half the standard dose and a dose increase of Avirodin to 1000 mg every 8 hours are recommended when rifabutin and Avirodin are coadministered. |
Sildenafil | ↑ sildenafil concentration (only the use of sildenafil at doses used for treatment of erectile dysfunction has been studied with Avirodin) | May result in an increase in PDE5 inhibitor-associated adverse events, including hypotension, syncope, visual disturbances, and priapism. Use of sildenafil for pulmonary arterial hypertension (PAH): Use of Revatio Use of sildenafil for erectile dysfunction: Sildenafil dose should not exceed a maximum of 25 mg in a 48-hour period in patients receiving concomitant Avirodin therapy. Use with increased monitoring for adverse events. |
Tadalafil | ↑ tadalafil concentration | May result in an increase in PDE5 inhibitor-associated adverse events, including hypotension, visual disturbances, and priapism. Use of tadalafil for pulmonary arterial hypertension (PAH): The following dose adjustments are recommended for use of Adcirca Co-administration of Adcirca in patients on Avirodin or co-administration of Avirodin in patients on Adcirca: Start at or adjust Adcirca to 20 mg once daily. Increase to 40 mg once daily based upon individual tolerability. Use of tadalafil for erectile dysfunction: Tadalafil dose should not exceed a maximum of 10 mg in a 72-hour period in patients receiving concomitant Avirodin therapy. Use with increased monitoring for adverse events. |
Vardenafil | ↑ vardenafil concentration | Vardenafil dose should not exceed a maximum of 2.5 mg in a 24-hour period in patients receiving concomitant Avirodin therapy. |
Venlafaxine | ↓ Avirodin concentration | In a study of 9 healthy volunteers, venlafaxine administered under steady-state conditions at 150 mg/day resulted in a 28% decrease in the AUC of a single 800 mg oral dose of Avirodin and a 36% decrease in Avirodin Cmax. Avirodin did not affect the pharmacokinetics of venlafaxine and ODV. The clinical significance of this finding is unknown. |
Carcinogenicity studies were conducted in mice and rats. In mice, no increased incidence of any tumor type was observed. The highest dose tested in rats was 640 mg/kg/day; at this dose a statistically significant increased incidence of thyroid adenomas was seen only in male rats. At that dose, daily systemic exposure in rats was approximately 1.3 times higher than daily systemic exposure in humans. No evidence of mutagenicity or genotoxicity was observed in in vitro microbial mutagenesis tests, in vitro alkaline elution assays for DNA breakage, in vitro and in vivo chromosomal aberration studies, and in vitro mammalian cell mutagenesis assays. No treatment-related effects on mating, fertility, or embryo survival were seen in female rats and no treatment-related effects on mating performance were seen in male rats at doses providing systemic exposure comparable to or slightly higher than that with the clinical dose. In addition, no treatment-related effects were observed in fecundity or fertility of untreated females mated to treated males.
Developmental toxicity studies were performed in rabbits, dogs (at doses up to 80 mg/kg/day), and rats (at doses up to 640 mg/kg/day). The highest doses in these studies produced systemic exposures in these species comparable to or slightly greater than human exposure. No treatment-related external, visceral, or skeletal changes were observed in rabbits or dogs. No treatment-related external or visceral changes were observed in rats. Treatment-related increases over controls in the incidence of supernumerary ribs (at exposures at or below those in humans) and of cervical ribs (at exposures comparable to or slightly greater than those in humans) were seen in rats. In all three species, no treatment-related effects on embryonic/fetal survival or fetal weights were observed.
In rabbits, at a maternal dose of 240 mg/kg/day, no drug was detected in fetal plasma 1 hour after dosing. Fetal plasma drug levels 2 hours after dosing were approximately 3% of maternal plasma drug levels. In dogs, at a maternal dose of 80 mg/kg/day, fetal plasma drug levels were approximately 50% of maternal plasma drug levels both 1 and 2 hours after dosing. In rats, at maternal doses of 40 and 640 mg/kg/day, fetal plasma drug levels were approximately 10 to 15% and 10 to 20% of maternal plasma drug levels 1 and 2 hours after dosing, respectively.
Avirodin was administered to Rhesus monkeys during the third trimester of pregnancy (at doses up to 160 mg/kg twice daily) and to neonatal Rhesus monkeys (at doses up to 160 mg/kg twice daily). When administered to neonates, Avirodin caused an exacerbation of the transient physiologic hyperbilirubinemia seen in this species after birth; serum bilirubin values were approximately fourfold above controls at 160 mg/kg twice daily. A similar exacerbation did not occur in neonates after in utero exposure to Avirodin during the third trimester of pregnancy. In Rhesus monkeys, fetal plasma drug levels were approximately 1 to 2% of maternal plasma drug levels approximately 1 hour after maternal dosing at 40, 80, or 160 mg/kg twice daily.
Hyperbilirubinemia has occurred during treatment with Avirodin. It is unknown whether Avirodin administered to the mother in the perinatal period will exacerbate physiologic hyperbilirubinemia in neonates.
There are no adequate and well-controlled studies in pregnant patients. Avirodin should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
A Avirodin dose of 800 mg every 8 hours (with zidovudine 200 mg every 8 hours and lamivudine 150 mg twice a day) has been studied in 16 HIV-infected pregnant patients at 14 to 28 weeks of gestation at enrollment (study PACTG 358). Given the substantially lower antepartum exposures observed and the limited data in this patient population, Avirodin use is not recommended in HIV-infected pregnant patients.
To monitor maternal-fetal outcomes of pregnant patients exposed to Avirodin, an Antiretroviral Pregnancy Registry has been established. Physicians are encouraged to register patients by calling 1-800-258-4263.
Studies in lactating rats have demonstrated that Avirodin is excreted in milk. Although it is not known whether Avirodin is excreted in human milk, there exists the potential for adverse effects from Avirodin in nursing infants. Mothers should be instructed to discontinue nursing if they are receiving Avirodin. This is consistent with the recommendation by the U.S. Public Health Service Centers for Disease Control and Prevention that HIV-infected mothers not breast-feed their infants to avoid risking postnatal transmission of HIV.
The optimal dosing regimen for use of Avirodin in pediatric patients has not been established. A dose of 500 mg/m2 every eight hours has been studied in uncontrolled studies of 70 children, 3 to 18 years of age. The pharmacokinetic profiles of Avirodin at this dose were not comparable to profiles previously observed in adults receiving the recommended dose. Although viral suppression was observed in some of the 32 children who were followed on this regimen through 24 weeks, a substantially higher rate of nephrolithiasis was reported when compared to adult historical data. Physicians considering the use of Avirodin in pediatric patients without other protease inhibitor options should be aware of the limited data available in this population and the increased risk of nephrolithiasis.
Clinical studies of Avirodin did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal or cardiac function and of concomitant disease or other drug therapy.
Nephrolithiasis/urolithiasis, including flank pain with or without hematuria, has been reported in approximately 12.4% (301/2429; range across individual trials: 4.7% to 34.4%) of patients receiving Avirodin at the recommended dose in clinical trials with a median follow-up of 47 weeks (range: 1 day to 242 weeks; 2238 patient-years follow-up). The cumulative frequency of nephrolithiasis events increases with duration of exposure to Avirodin; however, the risk over time remains relatively constant. Of the patients treated with Avirodin who developed nephrolithiasis/urolithiasis in clinical trials during the double-blind phase, 2.8% (7/246) were reported to develop hydronephrosis and 4.5% (11/246) underwent stent placement. Following the acute episode, 4.9% (12/246) of patients discontinued therapy.
Asymptomatic hyperbilirubinemia (total bilirubin ≥2.5 mg/dL), reported predominantly as elevated indirect bilirubin, has occurred in approximately 14% of patients treated with Avirodin. In <1% this was associated with elevations in ALT or AST.
Hyperbilirubinemia and nephrolithiasis/urolithiasis occurred more frequently at doses exceeding 2.4 g/day compared to doses ≤2.4 g/day.
Clinical adverse experiences reported in ≥2% of patients treated with Avirodin alone, Avirodin in combination with zidovudine or zidovudine plus lamivudine, zidovudine alone, or zidovudine plus lamivudine are presented in Table 10.
Study 028 Considered Drug-Related and of Moderate or Severe Intensity | Study ACTG 320 of Unknown Drug Relationship and of Severe or Life-threatening Intensity | |||||
Avirodin | Avirodin plus Zidovudine | Zidovudine | Avirodin plus Zidovudine plus Lamivudine | Zidovudine plus Lamivudine | ||
Adverse Experience | Percent (n=332) | Percent (n=332) | Percent (n=332) | Percent (n=571) | Percent (n=575) | |
Body as a Whole | ||||||
Abdominal pain | 16.6 | 16.0 | 12.0 | 1.9 | 0.7 | |
Asthenia/fatigue | 2.1 | 4.2 | 3.6 | 2.4 | 4.5 | |
Fever | 1.5 | 1.5 | 2.1 | 3.8 | 3.0 | |
Malaise | 2.1 | 2.7 | 1.8 | 0 | 0 | |
Digestive System | ||||||
Nausea | 11.7 | 31.9 | 19.6 | 2.8 | 1.4 | |
Diarrhea | 3.3 | 3.0 | 2.4 | 0.9 | 1.2 | |
Vomiting | 8.4 | 17.8 | 9.0 | 1.4 | 1.4 | |
Acid regurgitation | 2.7 | 5.4 | 1.8 | 0.4 | 0 | |
Anorexia | 2.7 | 5.4 | 3.0 | 0.5 | 0.2 | |
Appetite increase | 2.1 | 1.5 | 1.2 | 0 | 0 | |
Dyspepsia | 1.5 | 2.7 | 0.9 | 0 | 0 | |
Jaundice | 1.5 | 2.1 | 0.3 | 0 | 0 | |
Hemic and Lymphatic System | ||||||
Anemia | 0.6 | 1.2 | 2.1 | 2.4 | 3.5 | |
Musculoskeletal System | ||||||
Back pain | 8.4 | 4.5 | 1.5 | 0.9 | 0.7 | |
Nervous System/Psychiatric | ||||||
Headache | 5.4 | 9.6 | 6.0 | 2.4 | 2.8 | |
Dizziness | 3.0 | 3.9 | 0.9 | 0.5 | 0.7 | |
Somnolence | 2.4 | 3.3 | 3.3 | 0 | 0 | |
Skin and Skin Appendage | ||||||
Pruritus | 4.2 | 2.4 | 1.8 | 0.5 | 0 | |
Rash | 1.2 | 0.6 | 2.4 | 1.1 | 0.5 | |
Respiratory System | ||||||
Cough | 1.5 | 0.3 | 0.6 | 1.6 | 1.0 | |
Difficulty breathing/ dyspnea/ shortness of breath | 0 | 0.6 | 0.3 | 1.8 | 1.0 | |
Urogenital System | ||||||
Nephrolithiasis/urolithiasis | 8.7 | 7.8 | 2.1 | 2.6 | 0.3 | |
Dysuria | 1.5 | 2.4 | 0.3 | 0.4 | 0.2 | |
Special Senses | ||||||
Taste perversion | 2.7 | 8.4 | 1.2 | 0.2 | 0 |
In Phase I and II controlled trials, the following adverse events were reported significantly more frequently by those randomized to the arms containing Avirodin than by those randomized to nucleoside analogues: rash, upper respiratory infection, dry skin, pharyngitis, taste perversion.
Selected laboratory abnormalities of severe or life-threatening intensity reported in patients treated with Avirodin alone, Avirodin in combination with zidovudine or zidovudine plus lamivudine, zidovudine alone, or zidovudine plus lamivudine are presented in Table 11.
Study 028 | Study ACTG 320 | ||||
Avirodin | Avirodin plus Zidovudine | Zidovudine | Avirodin plus Zidovudine plus Lamivudine | Zidovudine plus Lamivudine | |
Percent (n=329) | Percent (n=320) | Percent (n=330) | Percent (n=571) | Percent (n=575) | |
Hematology | |||||
Decreased hemoglobin <7.0 g/dL | 0.6 | 0.9 | 3.3 | 2.4 | 3.5 |
Decreased platelet count <50 THS/mm3 | 0.9 | 0.9 | 1.8 | 0.2 | 0.9 |
Decreased neutrophils <0.75 THS/mm3 | 2.4 | 2.2 | 6.7 | 5.1 | 14.6 |
Blood chemistry | |||||
Increased ALT >500% ULN | 4.9 | 4.1 | 3.0 | 2.6 | 2.6 |
Increased AST >500% ULN | 3.7 | 2.8 | 2.7 | 3.3 | 2.8 |
Total serum bilirubin >250% ULN | 11.9 | 9.7 | 0.6 | 6.1 | 1.4 |
Increased serum amylase >200% ULN | 2.1 | 1.9 | 1.8 | 0.9 | 0.3 |
Increased glucose >250 mg/dL | 0.9 | 0.9 | 0.6 | 1.6 | 1.9 |
Increased creatinine >300% ULN | 0 | 0 | 0.6 | 0.2 | 0 |
Body As A Whole: redistribution/accumulation of body fat.
Cardiovascular System: cardiovascular disorders including myocardial infarction and angina pectoris; cerebrovascular disorder.
Digestive System: liver function abnormalities; hepatitis including reports of hepatic failure ; pancreatitis; jaundice; abdominal distention; dyspepsia.
Hematologic: increased spontaneous bleeding in patients with hemophilia ; acute hemolytic anemia.
Endocrine/Metabolic: new onset diabetes mellitus, exacerbation of pre-existing diabetes mellitus, hyperglycemia.
Hypersensitivity: anaphylactoid reactions; urticaria; vasculitis.
Musculoskeletal System: arthralgia, periarthritis.
Nervous System/Psychiatric: oral paresthesia; depression.
Skin and Skin Appendage: rash including erythema multiforme and Stevens-Johnson syndrome; hyperpigmentation; alopecia; ingrown toenails and/or paronychia; pruritus.
Urogenital System: nephrolithiasis/urolithiasis, in some cases resulting in renal insufficiency or acute renal failure, pyelonephritis with or without bacteremia ; interstitial nephritis sometimes with Avirodin crystal deposits; in some patients, the interstitial nephritis did not resolve following discontinuation of Avirodin; renal insufficiency; renal failure; leukocyturia, crystalluria; dysuria.
Increased serum triglycerides; increased serum cholesterol.
There have been more than 60 reports of acute or chronic human overdosage (up to 23 times the recommended total daily dose of 2400 mg) with Avirodin. The most commonly reported symptoms were renal (e.g., nephrolithiasis/urolithiasis, flank pain, hematuria) and gastrointestinal (e.g., nausea, vomiting, diarrhea).
It is not known whether Avirodin is dialyzable by peritoneal or hemodialysis.
The recommended dosage of Avirodin is 800 mg orally every 8 hours.
Avirodin must be taken at intervals of 8 hours. For optimal absorption, Avirodin should be administered without food but with water 1 hour before or 2 hours after a meal. Alternatively, Avirodin may be administered with other liquids such as skim milk, juice, coffee, or tea, or with a light meal, e.g., dry toast with jelly, juice, and coffee with skim milk and sugar; or corn flakes, skim milk and sugar.
To ensure adequate hydration, it is recommended that adults drink at least 1.5 liters (approximately 48 ounces) of liquids during the course of 24 hours.
Dose reduction of Avirodin to 600 mg every 8 hours should be considered when administering delavirdine 400 mg three times a day.
If Avirodin and didanosine are administered concomitantly, they should be administered at least one hour apart on an empty stomach.
Dose reduction of Avirodin to 600 mg every 8 hours is recommended when administering itraconazole 200 mg twice daily concurrently.
Dose reduction of Avirodin to 600 mg every 8 hours is recommended when administering ketoconazole concurrently.
Dose reduction of rifabutin to half the standard dose and a dose increase of Avirodin to 1000 mg every 8 hours are recommended when rifabutin and Avirodin are coadministered.
The dosage of Avirodin should be reduced to 600 mg every 8 hours in patients with mild-to-moderate hepatic insufficiency due to cirrhosis.
In addition to adequate hydration, medical management in patients who experience nephrolithiasis/urolithiasis may include temporary interruption (e.g., 1 to 3 days) or discontinuation of therapy.
Avirodin Capsules are supplied as follows:
No. 3756 - 200 mg capsules: semi-translucent white capsules coded "CRIXIVAN 200 mg" in blue. Available as:
NDC 0006-0571-43 unit-of-use bottles of 360.
No. 3758 - 400 mg capsules: semi-translucent white capsules coded "CRIXIVAN 400 mg" in green. Available as:
NDC 0006-0573-62 unit-of-use bottles of 180 (with desiccant)
Bottles: Store in a tightly-closed container at room temperature, 15-30°C (59-86°F). Protect from moisture.
Avirodin Capsules are sensitive to moisture. Avirodin should be dispensed and stored in the original container. The desiccant should remain in the original bottle.
Dist. by: Merck Sharp & Dohme Corp., a subsidiary of
MERCK & CO., INC., Whitehouse Station, NJ 08889, USA
For patent information: www.merck.com/product/patent/home.html
Copyright © 1996-2016 Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
All rights reserved.
Revised 09/2016
uspi-mk0639-c-1609r018
Avirodin® (indinavir sulfate) Capsules
Patient Information about
Avirodin (KRIK-sih-van)
for HIV (Human Immunodeficiency Virus) Infection
Generic name: Avirodin (in-DIH-nuh-veer) sulfate
ALERT: Find out about medicines that should NOT be taken with Avirodin®. Please also read the section "MEDICINES YOU SHOULD NOT TAKE WITH CRIXIVAN".
Please read this information before you start taking Avirodin. Also, read the leaflet each time you renew your prescription, just in case anything has changed. Remember, this leaflet does not take the place of careful discussions with your doctor. You and your doctor should discuss Avirodin when you start taking your medication and at regular checkups. You should remain under a doctor's care when using Avirodin and should not change or stop treatment without first talking with your doctor.
Avirodin is an oral capsule used for the treatment of HIV. HIV is the virus that causes AIDS (acquired immune deficiency syndrome). Avirodin is a type of HIV drug called a protease (PRO-tee-ase) inhibitor.
Avirodin is a protease inhibitor that fights HIV. Avirodin can help reduce your chances of getting illnesses associated with HIV. Avirodin can also help lower the amount of HIV in your body (called "viral load") and raise your CD4 (T) cell count. Avirodin may not have these effects in all patients.
Avirodin is usually prescribed with other anti-HIV drugs such as ZDV (also called AZT), 3TC, ddI, ddC, or d4T. Avirodin works differently from these other anti-HIV drugs. Talk with your doctor about how you should take Avirodin.
There are six important things you must do to help you benefit from Avirodin:
dry toast with jelly, juice, and coffee (with skim or non-fat milk and sugar if you want)
cornflakes with skim or non-fat milk and sugar
Do not take Avirodin at the same time as any meals that are high in calories, fat, and protein (for example - a bacon and egg breakfast). When taken at the same time as Avirodin, these foods can interfere with Avirodin being absorbed into your bloodstream and may lessen its effect.
Avirodin does not cure HIV infection or AIDS and you may continue to experience illnesses associated with HIV-1 infection, including opportunistic infections. You should remain under the care of a doctor when using Avirodin.
Avoid doing things that can spread HIV-1 infection.
Do not take Avirodin if you have had a serious allergic reaction to Avirodin or any of its components.
Talk to your doctor if:
Also talk to your doctor if you have:
Tell your doctor about any medicines you are taking or plan to take, including non-prescription medicines, herbal products including St. John's wort, or dietary supplements.
Can Avirodin be taken with other medications?
MEDICINES YOU SHOULD NOT TAKE WITH Avirodin
Oral VERSED® (midazolam) | HALCION® (triazolam) |
ORAP® (pimozide) | XANAX® (alprazolam) |
PROPULSID® (cisapride) | REVATIO® (sildenafil for the treatment of pulmonary arterial hypertension) |
CORDARONE® (amiodarone) | UROXATRAL® (alfuzosin) |
HISMANAL® (astemizole) | Ergot medications (e.g., Wigraine®, Cafergot®, D.H.E. 45®, Migranal®, Ergotrate®, and Methergine®) |
ZOCOR® (simvastatin) MEVACOR® (lovastatin) LATUDA® (lurasidone) |
Taking Avirodin with the above medications could result in serious or life-threatening problems (such as irregular heartbeat or excessive sleepiness).
In addition, you should not take Avirodin with the following:
Before you take VIAGRA® (sildenafil), CIALIS® (tadalafil), or LEVITRA® (vardenafil) with Avirodin, talk to your doctor about possible drug interactions and side effects. If you take any of these medicines together with Avirodin, you may be at increased risk of side effects such as low blood pressure, visual changes, and penile erection lasting more than 4 hours, which have been associated with sildenafil, tadalafil, and vardenafil. If an erection lasts longer than 4 hours, you should seek immediate medical assistance to avoid permanent damage to your penis. Your doctor can explain these symptoms to you.
MEDICINES YOU CAN TAKE WITH Avirodin
RETROVIR® (zidovudine, ZDV also called AZT) | EPIVIR (lamivudine, 3TC) |
ZERIT® (stavudine, d4T) | isoniazid (INH) |
BACTRIM®/SEPTRA® (trimethoprim/sulfamethoxazole) | DIFLUCAN® (fluconazole) |
BIAXIN® (clarithromycin) | ORTHO-NOVUM 1/35® (oral contraceptive) |
TAGAMET® (cimetidine) | Methadone |
VIDEX® (didanosine, ddI) - If you take Avirodin with VIDEX, take them at least one hour apart. | |
MYCOBUTIN® (rifabutin) - If you take Avirodin with MYCOBUTIN, your doctor may adjust both the dose of MYCOBUTIN and the dose of Avirodin. | |
NIZORAL® (ketoconazole) - If you take Avirodin with NIZORAL, your doctor may adjust the dose of Avirodin. | |
RESCRIPTOR® (delavirdine) - If you take Avirodin with RESCRIPTOR, your doctor may adjust the dose of Avirodin. | |
SPORANOX® (itraconazole) - If you take Avirodin with SPORANOX, your doctor may adjust the dose of Avirodin. | |
SUSTIVA (efavirenz) - If you take Avirodin with SUSTIVA, check with your doctor. | |
Intravenous VERSED® (midazolam) - If you take Avirodin with Intravenous VERSED®, your doctor may adjust the dose of VERSED®. |
Talk to your doctor about any medications you are taking.
Antipsychotics: Tell your doctor if you are taking antipsychotics (e.g., quetiapine).
Calcium Channel Blockers: Tell your doctor if you are taking calcium channel blockers (e.g., amlodipine, felodipine).
Antiarrhythmics: Tell your doctor if you are taking antiarrhythmics (e.g., quinidine).
Anticonvulsants: Tell your doctor if you are taking anticonvulsants (e.g., phenobarbital, phenytoin, or carbamazepine).
Steroids: Tell your doctor if you are taking steroids (e.g., dexamethasone).
Like all prescription drugs, Avirodin can cause side effects. The following is not a complete list of side effects reported with Avirodin when taken either alone or with other anti-HIV drugs. Do not rely on this leaflet alone for information about side effects. Your doctor can discuss with you a more complete list of side effects.
Some patients treated with Avirodin developed kidney stones. In some of these patients this led to more severe kidney problems, including kidney failure or inflammation of the kidneys or kidney infection which sometimes spread to the blood. Drinking at least six 8-ounce glasses of liquids (preferably water) each day should help reduce the chances of forming a kidney stone ( see How should I take Avirodin? ). Call your doctor or other health care provider if you develop kidney pains (middle to lower stomach or back pain) or blood in the urine.
Some patients treated with Avirodin have had rapid breakdown of red blood cells (hemolytic anemia) which in some cases was severe or resulted in death.
Some patients treated with Avirodin have had liver problems including liver failure and death. Some patients had other illnesses or were taking other drugs. It is uncertain if Avirodin caused these liver problems.
Diabetes and high blood sugar (hyperglycemia) have occurred in patients taking protease inhibitors. In some of these patients, this led to ketoacidosis, a serious condition caused by poorly controlled blood sugar. Some patients had diabetes before starting protease inhibitors, others did not. Some patients required adjustments to their diabetes medication. Others needed new diabetes medication.
In some patients with hemophilia, increased bleeding has been reported.
Severe muscle pain and weakness have occurred in patients taking protease inhibitors, including Avirodin, together with some of the cholesterol-lowering medicines called "statins". Call your doctor if you develop severe muscle pain or weakness.
Changes in body fat have been seen in some patients taking antiretroviral therapy. These changes may include increased amount of fat in the upper back and neck ("buffalo hump"), breast, and around the trunk. Loss of fat from the legs, arms and face may also happen. The cause and long term health effects of these conditions are not known at this time.
In some patients with advanced HIV infection (AIDS), signs and symptoms of inflammation from opportunistic infections may occur when combination antiretroviral treatment is started.
Clinical Studies
Increases in bilirubin (one laboratory test of liver function) have been reported in approximately 14% of patients. Usually, this finding has not been associated with liver problems. However, on rare occasions, a person may develop yellowing of the skin and/or eyes.
Side effects occurring in 2% or more of patients included: abdominal pain, fatigue or weakness, low red blood cell count, flank pain, painful urination, feeling unwell, nausea, upset stomach, diarrhea, vomiting, acid regurgitation, increased or decreased appetite, back pain, headache, dizziness, taste changes, rash, itchy skin, yellowing of the skin and/or eyes, upper respiratory infection, dry skin, and sore throat.
Swollen kidneys due to blocked urine flow occurred rarely.
Marketing Experience
Other side effects reported since Avirodin has been marketed include: allergic reactions; severe skin reactions; yellowing of the skin and/or eyes; heart problems including heart attack; stroke; abdominal swelling; indigestion; inflammation of the kidneys; decreased kidney function; inflammation of the pancreas; joint pain; depression; itching; hives; change in skin color; hair loss; ingrown toenails with or without infection; crystals in the urine; painful urination; numbness of the mouth; increased cholesterol; pain and difficulty moving shoulder.
Tell your doctor promptly about these or any other unusual symptoms. If the condition persists or worsens, seek medical attention.
This medication was prescribed for your particular condition. Do not use it for any other condition or give it to anybody else. Keep Avirodin and all medicines out of the reach of children. If you suspect that more than the prescribed dose of this medicine has been taken, contact your local poison control center or emergency room immediately.
This leaflet provides a summary of information about Avirodin. If you have any questions or concerns about either Avirodin or HIV, talk to your doctor.
Distributed by:
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
Whitehouse Station, NJ 08889, USA
For patent information: www.merck.com/product/patent/home.html
The trademarks depicted herein are owned by their respective companies.
Copyright © 1996-2016 Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
All rights reserved.
Revised 09/2016
usppi-mk0639-c-1609r018
NDC 0006-0571-43
Avirodin ®
(Indinavir Sulfate) Capsules
200 mg
ALERT
Find out about medicines that should NOT be taken
with Avirodin.
Note to Pharmacist:
Do not cover ALERT box with Pharmacy label.
Each capsule contains Avirodin 200 mg (corresponding to Avirodin
sulfate 250 mg). Store in a tightly closed container at room
temperature,15-30°C (59-86°F). Protect from moisture.
Avirodin Capsules are sensitive to
moisture and should be dispensed and
stored in the original container.
The desiccant should remain in the
original bottle.
USUAL
Dosage: See Package Insert.
Rx only
360 Capsules
Lot
Exp.
NDC 0006-0573-62
Avirodin ®
(Indinavir Sulfate) Capsules
400 mg
ALERT
Find out about medicines that should NOT be taken
with Avirodin.
Note to Pharmacist:
Do not cover ALERT box with Pharmacy label.
Each capsule contains Avirodin 400 mg (corresponding to Avirodin
sulfate 500 mg). Store in a tightly closed container at room
temperature,15-30°C (59-86°F).
Protect from moisture. Avirodin Capsules
are sensitive to moisture and should be
dispensed and stored in the original
container. The desiccant should remain
in the original bottle.
USUAL
Dosage: See Package Insert.
Rx only
180 Capsules
Lot
Exp.
Depending on the reaction of the Avirodin after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Avirodin not safe to drive or operate heavy machine after consumption. Meaning that, do not drive or operate heavy duty machines after taking the capsule if the capsule has a strange reaction on your body like dizziness, drowsiness. As prescribed by a pharmacist, it is dangerous to take alcohol while taking medicines as it exposed patients to drowsiness and health risk. Please take note of such effect most especially when taking Primosa capsule. It's advisable to consult your doctor on time for a proper recommendation and medical consultations.
Is Avirodin addictive or habit forming?Medicines are not designed with the mind of creating an addiction or abuse on the health of the users. Addictive Medicine is categorically called Controlled substances by the government. For instance, Schedule H or X in India and schedule II-V in the US are controlled substances.
Please consult the medicine instruction manual on how to use and ensure it is not a controlled substance.In conclusion, self medication is a killer to your health. Consult your doctor for a proper prescription, recommendation, and guidiance.
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The information was verified by Dr. Rachana Salvi, MD Pharmacology