Last Updated on February 19, 2017 by Dr.Derek Fhisher
Most popular brand: Crixivan
Active ingredient: Indinavir
Available dosage forms: 400 mg
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Indinavir general information
A few other truth about alcohol are extremely scary. This is definitely the most dangerous kind of alcoholism for the reason that it compromises your body’s capability to function properly. You can quit drinking alcohol and take a few pills that got a similar influence on the nervous system as alcohol. If you start drinking alcohol inside this state to relax, you’ll be hit with a double whammy. Of course your results can fluctuate so speak to your doctor today to see whether TADALAFIL is appropriate for you. Make certain the rehab center you approach has the infrastructure to supply personalized psychological and physical therapy agreeing with the needs of the alcoholic.
We’re living in the interval of perfection today. That is why women believe feel like they’re going crazy. I’m going to point out the man along with the woman within the relationship must do their research, communicate.
Alcohol poisoning is quite a real possibility for alcoholics and certainly will be fatal. Initially alcohol might not be an issue, as the drinks consumed are few. Parents’ drinking behavior might also bring about a teenager to begin drinking early in life. You’re influenced by your house environment and also your parents’ use of alcohol.
The ideal weapon against alcoholism is the capacity to be good decisions predicated on factual details. Information is frequently presented as alcoholism fact. This specialized diet is important since the different symptoms of the assorted phases of pancreatitis require several types of food. As the root cause is biological, it truly isn’t very simple to locate a fantastic solution for it.
As a way to quit drinking, you ought to maintain a diary of your own drinking. Even during the time they’re not drinking, alcoholics wouldn’t be able enough to concentrate on the work available. To begin with, when an individual has been drinking heavily for a very long time it’s often difficult to allow them to stop. Alcohol can force you to laugh or it may force you to cry, it can cause you to get lively or force you to sleepy, it can increase your confidence or cause you to get act the fool. It can assist you to battle peer pressure in regards to social drinking. Forget the vino and following dinner coffee and cigarette and instead have a walk, pay attention to your breathing when walking and have a tiny glass of (ice) water when finished.
Discovering the characteristics of alcoholism after they appear can alter the plan of life or death. The reality is there are two major sorts of alcoholism. I’ve observed that different kinds of alcohol can affect you much more than many others. It was discovered that women have a greater mortality rate on account of alcoholism than man do. This could be caused from a diet full of purines, particularly those containing organ meats and fish.
People afflicted by acute pancreatitis frequently demand a trip to the emergency room along with a stay within the intensive care unit. There are particular differences between penicillin and the majority of other drugs. So while conventional medicine is useful in treating pancreatitis, a prosperous general treatment of pancreatitis asks a team approach. This shouldn’t be used at all as a stand-in for medical advice or care. When budget isn’t of any concern, many people will appear into treatment options both near and wide. Your personal doctor will prescribe the dose that’s best for you.
It may appear difficult to believe that within the calendar year 2016, there continue to be places within this nation thatalcohol prohibition remains on the books in certain states. Usually every time a rumor starts flying, there’s no less than a tiny truth to it. Of course some people today have a problem to it and some don’t. There’s a reason which I wrote this short article.
Alcohol has evolved into a destructive force. Later, within the sleep cycle, sleep may be disturbed. Peer drinking and pressure also have been connected to teenage drinking. Alcohol will not mimic a neurotransmitter.
You’re about to learn. The reply is most likely yes. A number of the modest hand-crafted bourbons can become up there so far as alcohol content goes, too. For the very first step, you are going to paint a thin coat of rubbing alcohol on the tile.
Large amounts of alcohol can maintain a person asleep longer, but drinking big amounts of alcohol has its very own negative results. Even in little doses, alcohol can lead to a spasm within the Sphincter of Oddi. Morphine, for instance, mimics the neurotransmitter beta-endorphin–a all-natural painkiller found within the brain. The simplest secondary alcohol is isopropanol, whilst butanol is a basic tertiary alcohol.
All that before an addict is prepared to think about eliminating sugar. For taking away the effects of the hangover, the juice of the lemon or orange will be quite powerful. Acidic alcoholic beverages like wine, vodka and whiskeys ought to be avoided. Drink for taste in place of effect.
This is recognized as homeostasis. Fewer cells will remain to be necessary connections within the brain. There are better, all organic solutions that will perform the job. They’ll ask you a lot of distinctive questions and might even perform a succession of medical tests.
Therapeutic substance indinavir sulfate
The funds for the treatment of HIV – infection
The nosological classification (ICD – 10)
B20 – B24 disease caused by human immunodeficiency virus [HIV]
The characteristic substance indinavir sulfate
An inhibitor of HIV – protease. White or almost white hygroscopic crystalline powder. It is soluble in water and methanol.
Mode of action – an antiviral that inhibits HIV protease. Inhibits HIV – protease – an enzyme required for the proteolytic cleavage of polypeptides – precursors and formation of functional viral proteins. By binding to the active site of the protease, indinavir inhibits its enzymatic activity, thereby preventing cleavage of viral polyprotein, which leads to the formation of immature viral particles unable to infect other kletki.Otsenka indinavir antiretroviral activity in vitro showed that in concentrations of 25 to 100 nM he 95% inhibited HIV-1 replication in cell cultures of a number of lymphoid and monocyte and lymphocyte culture infected with laboratory strains and primary clinical isolates of HIV-1, including isolates resistant to nucleoside and non-nucleoside inhibitors of HIV-1 reverse transcriptase. In cell culture experiments manifested synergistic antiretroviral activity against HIV-1 in combination with reverse transcriptase inhibitors (zidovudine, didanosine). The relationship between the sensitivity of HIV-1 in vitro to indinavir and suppression of virus replication in the human body is not obtained in some patients ustanovlena.Ot HIV-1 isolates with reduced susceptibility to indinavir. Viral resistance correlates with the accumulation of mutations in the viral genome, resulting in the expression of the substituted amino acid residues in the enzyme (protease virus). Identification of at least 11 amino acid residues in positions this enzyme, which substitution is accompanied by the development of resistance. Moreover, resistance to the inhibitor are not mediated single and multiple and diverse substitutions. In general, a higher level of resistance is the result of co-expression of greater numbers of substitutions in the 11 identified polozheniyah.Otmechena cross-resistance of varying severity between indinavir and other inhibitors of HIV-1 protease. In studies with ritonavir, saquinavir and amprenavir severity and range of cross-resistance varied. The degree of cross-resistance increases with the accumulation of substitutions of amino acid residues that are associated with resistance. Investigation 29 isolates from patients treated with indinavir, it showed that they were all resistant to ritonavir. Among indinavir – resistant HIV-1 isolates 63% were resistant to saquinavir, and 81% – to amprenaviru.Posle oral (fasting) is rapidly absorbed from the gastrointestinal tract. Time to Cmax was 0.8 ± 0.3 h (n = 11). The dose range 200-1000 mg indinavir concentration increases proportionally with dose not plasma. Reception with high-calorie food rich in fats and proteins led to a reduction of absorption, with AUC and Cmax were reduced by approximately 80% (n = 10). Receiving a light meal (eg, dried toast with jelly, apple juice, coffee with skim milk and sugar, cornflakes) practically did not cause changes in absorption. Binding to plasma proteins is 60% .After oral administration in healthy volunteers labeled carbon (14C) of indinavir 400 mg 83 ± 1% of the total radioactivity was detected in the feces (n = 4), 19 ± 3% – in urine (n = 6 ) are unchanged to – 19.1% and 9.4%, respectively. Seven metabolites have been identified, one conjugate with glucuronic acid and oxidation products 6. In in vitro studies on liver microsomes showed that major isoenzyme cytochrome P450 involved in the oxidative metabolism of indinavir is CYP3A4. Less than 20% of indinavir is excreted in the urine in unchanged form. The mean renal excretion of unchanged substance 10,4 ± 4,9% (n = 10) and 12,0 ± 4,9% (n = 10) after administration of a single dose of 700 mg and 1000 mg, respectively. T1 / 2 was 1.8 ± 0.4 h (n = 10). When receiving multiple doses of 800 mg every 8 hours, no significant accumulation nablyudaetsya.Proniknovenie indinavir across the placental barrier significantly in rats and dogs, but small rabbits. Indinavir is released rapidly into the milk of lactating krys.Zavisimost pharmacokinetic parameters of certain faktorovPechenochnaya failure. In patients with mild to moderate hepatic impairment and clinically established cirrhosis showed a decrease in indinavir metabolism, manifested in the increase of AUC by about 60% after a single dose of 400 mg (n = 12), raising the T1 / 2 to 2,8 ± 0,5 h. The pharmacokinetics of indinavir in patients with severe hepatic impairment is not izuchalas.Pochechnaya failure. The pharmacokinetics of indinavir in patients with renal insufficiency not izuchalas.Pol. Clinically significant differences between the pharmacokinetic parameters (including AUC, Cmax) depending from the floor vyyavleno.Rasa. The pharmacokinetic parameters of indinavir in 42 Caucasians (26 HIV – positive) and 16 blacks (4 HIV – positive) were sravnimy.V two clinical trials of indinavir in combination with antiretroviral agents of approximately 1 year demonstrated a decrease risk of AIDS – related illnesses or death, as well as long-term suppression of viral RNK.Kantserogennost, mutagenicity, carcinogenicity fertilnostOtsenka effect on indinavir was conducted in mice and rat studies. There was no increase in the incidence of tumors in mice. At the highest dose tested in rats (640 mg / kg / day) had a statistically significant increase in the incidence of thyroid tumors in male rats. There were no mutagennocti or genotoxicity in some in vitro tests and in vivo, effects on crossability, fertility and embryonic survival of offspring in rats at doses providing systemic exposure comparable to or slightly greater than when using therapeutic doses in cheloveka.Beremennost. Indinavir toxicity study was performed in rabbits, dogs and rats at doses providing systemic exposure that is comparable to or slightly greater than that of a man. There were no external or visceral disorders, skeletal changes in rabbits and dogs. The rats showed improvement (compared to control) the frequency of formation of excess edges (when exposed to equal to or less than human) and the neck rib (upon exposure comparable to or greater than human). There were no effect of indinavir on embryonic / fetal survival or fetal growth in all three vidov.Vvedenie indinavir newborn monkeys – rhesus (at doses up to 160 mg / kg 2 times a day) caused a transient increase in physiological hyperbilirubinemia (bilirubin serum levels of about 4 times higher than control). Introduction indinavir monkeys (at the same doses) to the uterus in the III trimester of pregnancy did not cause such changes in the newborn. At doses of 40, 80 or 160 mg / kg two times a day in monkeys indinavir fetal blood levels were approximately 1-2% of the levels in the maternal organism.
Application of the substance indinavir sulfate
According to the Physicians Desk Reference (2003), indinavir sulfate in combination with antiretroviral agents is indicated for the treatment of HIV – infection.
Hypersensitivity; can not be administered concurrently with terfenadine, cisapride, astemizole, triazolam, midazolam or drugs based on extracts of ergot (indinavir inhibition of CYP3A4 may lead to increased concentrations of these drugs in the blood that can cause serious or life-threatening reaction).
Restrictions on the use
Pregnancy, breast-feeding, child age (safety and efficacy of the children are not identified).
Pregnancy and breastfeeding
When pregnancy is possible only if the effect of therapy outweighs the potential risk to the fetus (adequate and well-controlled studies in pregnant women have not performed) .Kategoriya effects on the fetus by FDA – C.Sposobnost indinavir excreted is not defined in the milk of nursing women. In experimental studies have demonstrated that indinavir passes into breast milk in lactating rats. At the time of treatment should stop breastfeeding (because of the possibility of serious adverse effects in infants who are breastfed) .Neizvestno reinforces whether indinavir received by his mother in the perinatal period, physiological hyperbilirubinemia in neonates.
Side effects of substance indinavir sulfate
The side effects associated with the intake of indinavir sulfate and watched by more than 2% of patients (based on double-blind, multicenter, randomized, the finished test carried out in Brazil – Study 028), are presented in Table 1. Table 1Klinicheski significant side effects moderate or severe degrees of severity, occurs in ≥2% of patients (Study 028)
Systems organism / Side Effects
0.3V through a series of clinical trials, approximately 12.4% (301/2429) of patients treated with indinavir sulfate in recommended doses, it has been marked nephrolithiasis, including flank pain with hematuria (including microhematuria) or without (ranging from 4.7% to 34.4% in different studies); Medium term clinical trials was 47 weeks (range 1 day to 242 weeks, 2,238 patients completed the study). In clinical trials during the double-blind phase in the development of nephrolithiasis during treatment with indinavir sulfate in 2.8% (7/246) of patients developed hydronephrosis, in 4.5% (11/246) – mounted stent. After acute seizures in 4.9% (12/246) of patients treated was otmeneno.Pri indinavir sulfate treatment of asymptomatic cases of hyperbilirubinemia observed (total bilirubin ≥2,5 mg / dL), which is manifested mainly indirect bilirubin increase (about 14%) and less than 1% of cases accompanied by an increase in ALT or AST.Giperbilirubinemiya and nephrolithiasis occurred with greater frequency when receiving doses greater than 2.4 g / day (compared with taking doses ≤2,4 g / day) .Some laboratory parameters presented in table 2. table 2No some laboratory tests and severe life-threatening severity (Study 028)
indinavir sulfate (n = 329)
indinavir sulfate + zidovudine (n = 320)
Decrease hemoglobin less than 70 g / l
The decrease in platelet count less than 50 x 109 / L
The decrease in neutrophils less than 0.75 x 109 / l
Increase in ALT of more than 500% ULN *
Increased AST more than 500% ULN
The total serum bilirubin more than 250% ULN
Increase of serum amylase more than 200% ULN
Increase glucose more than 13.875 mmol / l
Increase in creatinine of more than 300% ULN
0,6 * ULN – the upper limit normyDannye postmarketing issledovaniyOrganizm overall redistribution / accumulation of body fat in the neck, chest, abdomen and retroperitoneal oblasti.Serdechno – vascular system and blood: cardio – vascular diseases, including myocardial infarction, angina pectoris, cerebrovascular accident, increase in the frequency of spontaneous bleeding in patients with hemophilia, acute hemolytic anemia (see “Precautions”.) Gastro – intestinal tract:. hepatic dysfunction, hepatitis, liver failure (see “Precautions”.) pancreatitis, abdominal distention, jaundice, dispepsiya.Allergicheskie reactions: anaphylactoid reactions, urticaria, vaskulit.Nervnaya system and sensory organs: oral paresthesia, depressiya.Kozha and its appendages: rash, including erythema multiforme and Stevens – Johnson syndrome, hyperpigmentation, alopecia, ingrown nails toes and / or paronychia, zud.Mochepolovaya system: nephrolithiasis, including with impaired renal function, including acute renal failure (see “Precautions”.), pyelonephritis with or without bacteremia, crystalluria; interstitial nephritis, sometimes with the deposition of crystals of indinavir; in some patients, interstitial nephritis did not stop after taking indinavir sulfate; leucocyturia, dizuriya.Prochie: newly diagnosed diabetes mellitus, exacerbation of existing diabetes mellitus, hyperglycemia (see “Precautions”.), arthralgia, elevated serum triglycerides, increased serum cholesterol.
It should not be administered concurrently with terfenadine, cisapride, astemizole, triazolam, midazolam or drugs based on extracts of ergot (inhibition of indinavir CYP3A4 enzyme cytochrome P450 can lead to increased concentrations of these drugs in the blood and to the development of severe or life-threatening reactions). rifampicin is a potent inducer of CYP3A4 and markedly reduces plasma concentrations of indinavir (should not be administered simultaneously) The reaction of indinavir with drugs that are less potent inducers of CYP3A4, than rifampicin, for example, phenobarbital, phenytoin, carbamazepine and dexamethasone not studied; by sharing a caution should be exercised (possibly decrease plasma concentrations of indinavir) .Preparaty containing St. John’s wort extract, reduce the plasma levels of indinavir (may decrease the effectiveness of treatment) .Odnovremennoe appointment rifabutin and indinavir is accompanied by increased concentrations of rifabutin and a decrease in plasma concentrations of indinavir (you must decrease dose of rifabutin and dose increase of indinavir) .In connection with the increasing concentration of indinavir in the plasma, while the appointment of indinavir and ketoconazole should consider dose reduction indinavira.Itrakonazol CYPZA4 is an inhibitor, which increases plasma concentrations of indinavir (while the appointment is required a dose reduction of indinavir) .If simultaneous appointment of indinavir and efavirenz due to enzyme induction decreases the concentration of indinavir in the blood plasma (necessary to increase the dose of indinavir) .Po results of a published study in HIV – infected men (n = 6), the combined use of indinavir and sildenafil citrate lead to mutual increasing concentration of indinavir (including AUC in the range of 0-8 hours after administration – by 11%, Cmax – 48%) and sildenafil (AUC was increased by 340%) in the blood (it should be very careful because of the increased risk of adverse effects of sildenafil) .Odnovremennoe use of indinavir sulfate lovastatin or simvastatin is not recommended. Caution must be exercised when taking protease inhibitors (including indinavir sulfate) at the same time and with other inhibitors of HMG – KoA – reductase inhibitors metabolized with the participation of CYP3A4 (eg, atorvastatin calcium or sodium cerivastatin), because this combination of drugs may increase the risk of myopathy, including rabdomioliz.V studies no clinically significant interactions with the following drugs: zidovudine, zidovudine / lamivudine, trimethoprim / sulfamethoxazole, fluconazole, isoniazid, clarithromycin, methadone, cimetidine, quinidine, norethisterone / ethinylestradiol – containing birth control.
There are more than 60 reports of acute or chronic overdose in humans (including when receiving doses up to 23 times the recommended daily dose of 2.4 g). In most cases, the symptoms were observed kidney (nephrolithiasis, flank pain, hematuria) and gastro – intestinal symptoms (nausea, vomiting, diarrhea) .Neizvestno whether peritoneal or hemodialysis is effective.
Dosing and Administration
Inside for 1 hour before or 2 hours after eating a small amount of water or the like. Liquid (skim milk, juice, coffee, tea) or simultaneously with a light meal (corn flakes with skim milk and sugar, etc. ).. The recommended dose – 2.4 g / day (800 mg every 8 hours).
Precautions substance indinavir sulfate
When treatment with indinavir nephrolithiasis develops. In some cases, nephrolithiasis accompanied by renal impairment or acute renal failure, pyelonephritis with or without bacteremia. If signs or symptoms of nephrolithiasis, including flank pain with hematuria (including microscopic hematuria) or without, you should consider a temporary suspension (eg 1-3 days) or discontinuation of therapy. All patients during treatment is recommended adequate hydration (at least 1.5 liters of fluid per day) .During postmarketing observations in patients treated with indinavir, it was marked by rare cases of interstitial nephritis with medullary calcification and cortical atrophy observed in patients with asymptomatic severe leukocyturia (more than 100 cells / field of view). Patients with severe asymptomatic leukocyturia need further obsledovanii.Imeyutsya reports on the development of acute hemolytic anemia, including
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