Atazanavir Krka: Uses, Dosage & Side Effects

What Is Atazanavir Krka and What Is It Used For?

Atazanavir Krka contains the active substance atazanavir, which belongs to the class of medicines known as HIV protease inhibitors (PIs). Protease inhibitors are a cornerstone of antiretroviral therapy and have been instrumental in transforming HIV from a fatal diagnosis into a manageable chronic condition. Atazanavir was originally developed by Bristol-Myers Squibb and first approved by the U.S. Food and Drug Administration (FDA) in 2003 under the brand name Reyataz. Atazanavir Krka is a generic version manufactured by KRKA, containing the same active substance in bioequivalent formulation.

HIV (human immunodeficiency virus) is a retrovirus that infects and destroys CD4+ T-lymphocytes, a critical component of the adaptive immune system. Without treatment, HIV progressively depletes CD4+ cells over years, leading to acquired immunodeficiency syndrome (AIDS) and vulnerability to opportunistic infections and malignancies. Modern antiretroviral therapy (ART) suppresses HIV replication to undetectable levels, preserves immune function, prevents progression to AIDS, restores quality of life, and dramatically reduces the risk of transmitting the virus to others. The concept that people with an undetectable viral load cannot transmit HIV sexually is encapsulated in the well-established U=U (Undetectable = Untransmittable) principle, endorsed by the World Health Organization (WHO) and major medical organizations worldwide.

Atazanavir works by selectively inhibiting HIV-1 protease, an aspartyl protease enzyme essential for the viral replication cycle. During HIV replication, the protease enzyme cleaves large polyprotein precursors (Gag and Gag-Pol) into individual structural proteins and enzymes needed to assemble new infectious viral particles (virions). When atazanavir blocks the protease, immature, non-infectious viral particles are produced that cannot go on to infect other cells. This mechanism is highly specific to the viral protease and does not significantly affect human aspartyl proteases at therapeutic concentrations.

In clinical practice, atazanavir is always used as part of a combination antiretroviral therapy (cART) regimen, typically consisting of two nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) plus atazanavir boosted with either ritonavir or cobicistat. Boosting with ritonavir or cobicistat inhibits the CYP3A4-mediated metabolism of atazanavir, resulting in higher and more sustained plasma concentrations that allow once-daily dosing and improve the drug’s pharmacokinetic profile. This pharmacokinetic enhancement is essential for reliable viral suppression.

Atazanavir has several distinctive clinical advantages that have maintained its place in treatment guidelines. It is associated with a favorable metabolic profile compared with some older protease inhibitors, including less impact on blood lipid levels (cholesterol and triglycerides). It is dosed once daily, which supports adherence—a critical factor in HIV treatment success. Additionally, atazanavir has a relatively high genetic barrier to resistance, meaning the virus must accumulate multiple mutations before it can escape the drug’s suppressive effect.

What Should You Know Before Taking Atazanavir Krka?

Atazanavir is a powerful and effective antiretroviral medication, but it requires careful medical supervision before and during treatment. Your HIV specialist will conduct a thorough assessment including liver function tests, kidney function tests, bilirubin levels, viral load measurement, CD4+ cell count, and a complete review of all concomitant medications and supplements. Several important clinical considerations must be addressed before treatment begins.

Contraindications

Atazanavir must not be used in the following situations:

• Hypersensitivity: Known allergy to atazanavir or any of the capsule’s excipients.
• Severe hepatic impairment: Patients with severe liver disease (Child-Pugh Class C) must not take atazanavir because drug metabolism is significantly impaired, leading to dangerously elevated drug levels.
• Contraindicated co-medications: Several medicines must never be taken with atazanavir due to the risk of life-threatening interactions, including rifampicin, St John’s wort (Hypericum perforatum), simvastatin, lovastatin, ergot alkaloids (ergotamine, dihydroergotamine), quetiapine, lurasidone, triazolam, oral midazolam, pimozide, sildenafil when used for pulmonary arterial hypertension, lomitapide, and certain hepatitis C antivirals depending on the combination.

Warnings and Precautions

Atazanavir treatment requires awareness of several important clinical issues. Hyperbilirubinemia (elevated bilirubin) is the most characteristic effect of atazanavir, occurring in a majority of patients. Atazanavir inhibits the UGT1A1 enzyme that conjugates bilirubin, leading to elevated unconjugated (indirect) bilirubin levels. This manifests as yellowing of the skin and eyes (jaundice) and scleral icterus. While this is a cosmetic concern and does not indicate liver toxicity or damage, it can be distressing for patients and may affect adherence. The hyperbilirubinemia reverses upon discontinuation of atazanavir.

Nephrolithiasis (kidney stones) and cholelithiasis (gallstones) have been reported in patients receiving atazanavir. Patients should be advised to maintain adequate hydration and report any flank pain, hematuria (blood in urine), or symptoms suggestive of urinary obstruction. If kidney stones occur, temporary interruption or permanent discontinuation of atazanavir may be considered.

Cardiac conduction abnormalities, specifically prolongation of the PR interval on the electrocardiogram (ECG), have been observed with atazanavir. Most patients are asymptomatic, but caution is warranted in patients with pre-existing conduction disease, those taking other PR-prolonging medications, or those with underlying structural heart disease. Cases of first-degree, second-degree, and rarely third-degree atrioventricular (AV) block have been reported.

As with all antiretroviral therapy, immune reconstitution inflammatory syndrome (IRIS) may occur after starting atazanavir-based treatment. IRIS develops when the recovering immune system mounts an inflammatory response against previously latent or subclinical infections (such as Mycobacterium avium complex, cytomegalovirus, Pneumocystis jirovecii, or tuberculosis). Symptoms of IRIS typically appear in the first weeks to months of treatment and may require additional medical management.

Pregnancy and Breastfeeding

The use of atazanavir during pregnancy requires careful clinical judgment by an experienced HIV specialist. Atazanavir crosses the placenta, and pharmacokinetic studies have demonstrated reduced atazanavir exposure during the second and third trimesters due to pregnancy-related physiological changes, which may necessitate dose adjustment and more frequent viral load monitoring. Some international guidelines include atazanavir/ritonavir as an alternative protease inhibitor option during pregnancy when preferred regimens are not suitable.

A key concern with atazanavir use in pregnancy is neonatal hyperbilirubinemia. Because atazanavir inhibits UGT1A1 and crosses the placenta, it may exacerbate the physiological jaundice commonly seen in newborns, particularly premature infants whose bilirubin-conjugating capacity is already immature. Severe neonatal hyperbilirubinemia can potentially lead to kernicterus (bilirubin encephalopathy) if untreated. Neonates born to mothers receiving atazanavir should be closely monitored for hyperbilirubinemia.

Breastfeeding is generally not recommended for women living with HIV in resource-rich settings due to the risk of HIV transmission through breast milk. In resource-limited settings where the benefits of breastfeeding may outweigh the risks, WHO recommends that mothers on suppressive ART can breastfeed while continuing treatment, but this decision should be made with expert medical guidance. Atazanavir is excreted in breast milk.

How Does Atazanavir Krka Interact with Other Drugs?

Atazanavir is one of the most interaction-prone antiretroviral medicines, requiring meticulous attention to co-medications. It is primarily metabolized by the cytochrome P450 3A4 (CYP3A4) enzyme and is also a moderate inhibitor of CYP3A4 and a potent inhibitor of UGT1A1. When boosted with ritonavir (a potent CYP3A4 inhibitor), the interaction profile intensifies further. Additionally, atazanavir’s absorption is pH-dependent, meaning that any medication or condition that raises gastric pH can significantly reduce atazanavir blood levels and potentially lead to virological failure and resistance development.

Drug interaction checking is an essential component of HIV care. Before prescribing any new medication—including over-the-counter medicines, supplements, and herbal products—to a patient receiving atazanavir, healthcare providers should consult updated drug interaction databases. Patients should always inform all their healthcare providers (not just their HIV specialist) that they are taking atazanavir/ritonavir.

Major Interactions (Contraindicated)

Important Interactions Requiring Dose Adjustment or Monitoring

What Is the Correct Dosage of Atazanavir Krka?

Atazanavir dosing depends on the patient’s age, weight, treatment history, and whether a pharmacokinetic enhancer (booster) is used. In virtually all clinical scenarios today, atazanavir is administered with a booster (ritonavir or cobicistat) to ensure adequate and sustained drug levels. The following dosing recommendations are based on the EMA-approved Summary of Product Characteristics and major international HIV treatment guidelines.

Adults

It is crucial that atazanavir is taken with food, as food significantly enhances absorption. A meal or substantial snack increases both the extent (AUC) and peak concentration (Cmax) of atazanavir. Taking the medicine on an empty stomach results in substantially lower and more variable drug levels, which may compromise viral suppression. Patients should aim to take their dose at approximately the same time each day to maintain consistent drug levels throughout the 24-hour dosing interval.

Children (6 years and older, ≥15 kg)

Pediatric dosing of atazanavir is weight-based and must always be administered with ritonavir. The capsule formulation is suitable for children who can swallow capsules. The following table summarizes the recommended weight-based dosing:

Elderly

There is limited clinical experience with atazanavir in patients over 65 years of age. No specific dose adjustment is recommended based on age alone. However, elderly patients are more likely to have decreased hepatic or renal function and may be taking multiple medications, requiring careful attention to potential drug interactions and monitoring for adverse effects. HIV specialists should consider the patient’s overall clinical context, including comorbidities and polypharmacy, when prescribing atazanavir to older adults.

Hepatic Impairment

Atazanavir is extensively metabolized by the liver. Patients with moderate hepatic impairment (Child-Pugh Class B) may require dose reduction or closer monitoring. Atazanavir is contraindicated in severe hepatic impairment (Child-Pugh Class C). Patients with chronic hepatitis B or C co-infection are at increased risk of hepatic decompensation and should have liver function monitored more frequently.

Missed Dose

If a dose is missed and it has been less than 6 hours since the scheduled time, the patient should take the dose as soon as possible with food and continue the regular schedule. If more than 6 hours have passed, the missed dose should be skipped and the next dose taken at the usual time. Patients must never take a double dose to make up for a forgotten dose, as this increases the risk of side effects without providing additional benefit. Consistent adherence is essential for maintaining viral suppression and preventing resistance.

Overdose

Limited experience with overdose has been reported. Expected manifestations would include an extension of the known side effects, particularly jaundice (due to UGT1A1 inhibition) and possible cardiac effects (PR prolongation). There is no specific antidote for atazanavir. Treatment is supportive and should include monitoring of vital signs, ECG monitoring, and standard supportive measures. Atazanavir is highly protein-bound (approximately 86%) and is unlikely to be significantly removed by hemodialysis. In any suspected overdose, contact a poison control center or seek emergency medical attention.

What Are the Side Effects of Atazanavir Krka?

Like all medicines, atazanavir can cause side effects, although not everybody experiences them. The most distinctive side effect of atazanavir is unconjugated hyperbilirubinemia, which occurs because atazanavir inhibits the UGT1A1 enzyme responsible for bilirubin conjugation. This results in elevated indirect bilirubin levels and clinical jaundice (yellowing of the skin and whites of the eyes). This effect is mechanistically similar to Gilbert syndrome, a benign inherited condition affecting bilirubin metabolism. Although cosmetically bothersome, atazanavir-related hyperbilirubinemia is not associated with liver damage and reverses upon drug discontinuation.

It is important to distinguish atazanavir-associated jaundice from hepatotoxic jaundice. In atazanavir-induced hyperbilirubinemia, liver transaminases (ALT, AST) remain normal or only mildly elevated, and the elevated bilirubin is predominantly unconjugated (indirect). If conjugated (direct) bilirubin is elevated or liver enzymes are significantly raised, alternative causes of liver injury should be investigated promptly.

The side effect profile presented below is based on clinical trial data and post-marketing surveillance reports from the EMA-approved Summary of Product Characteristics. Side effects are classified by frequency according to the standard MedDRA convention.

Patients should report any new or worsening symptoms to their healthcare provider. In particular, seek immediate medical attention if you experience severe abdominal or flank pain (possible kidney stones or pancreatitis), severe skin rash with blistering or peeling, difficulty breathing or swelling of the face and throat (allergic reaction), or symptoms of cardiac arrhythmia such as palpitations, dizziness, or fainting.

The lipodystrophy syndrome (body fat redistribution) is a class effect associated with protease inhibitor therapy, though atazanavir may have less metabolic impact than some older protease inhibitors. Fat redistribution may include increased abdominal fat (central adiposity), dorsocervical fat pad enlargement (buffalo hump), peripheral fat wasting, breast enlargement, and facial lipoatrophy. Metabolic changes including insulin resistance, hyperglycemia, hyperlipidemia, and hyperlactatemia are also observed with antiretroviral therapy.

How Should You Store Atazanavir Krka?

Proper storage of antiretroviral medicines is important to maintain their effectiveness and safety throughout the treatment course. Atazanavir Krka 150 mg hard capsules should be stored at a temperature not exceeding 25°C (77°F). The capsules should be kept in their original container or blister pack to protect them from moisture, as humidity can affect the stability and integrity of the capsule shell and its contents.

Do not store Atazanavir Krka in the bathroom or near a sink where it may be exposed to humidity. Avoid storing the medicine in direct sunlight or near heat sources. Keep the container tightly closed when not in use. If you use a pill organizer, avoid transferring capsules to the organizer more than one week in advance, and ensure the organizer is kept in a cool, dry place.

Always check the expiry date before taking a dose. Do not use Atazanavir Krka after the expiry date stated on the carton and blister or container after “EXP”. The expiry date refers to the last day of that month. Expired medicines may not work effectively and could potentially be harmful.

Keep this medicine out of the sight and reach of children, as accidental ingestion could be dangerous. Do not dispose of medicines via household waste or wastewater. Ask your pharmacist about how to dispose of medicines that you no longer need. Proper disposal helps protect the environment and prevents accidental exposure to others.

What Does Atazanavir Krka Contain?

Active Ingredient

The active ingredient is atazanavir. Each hard capsule contains atazanavir sulfate equivalent to 150 mg of atazanavir. Atazanavir sulfate is an azapeptide HIV-1 protease inhibitor with the molecular formula C₃₈H₅₂N₆O₇·H₂SO₄. It is a white to pale yellow powder that is slightly soluble in water at neutral pH.

Inactive Ingredients (Excipients)

The inactive ingredients in Atazanavir Krka capsules include excipients necessary for the manufacturing process, capsule integrity, and stability. Typical excipients for atazanavir hard capsule formulations include:

• Crospovidone (disintegrant)
• Lactose monohydrate (filler)
• Magnesium stearate (lubricant)
• Gelatin (capsule shell)
• Titanium dioxide (E171) (opacifier)
• Indigo carmine (E132) (colorant)
• Iron oxide yellow (E172) (colorant)

Patients with known hypersensitivity to any of the excipients listed should consult their pharmacist or doctor before taking this medicine. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency, or glucose-galactose malabsorption should note the lactose content and discuss with their healthcare provider.

Appearance

Atazanavir Krka 150 mg hard capsules are opaque capsules with a distinctive colored cap and body for identification. Each capsule is printed with dosage strength identification. The capsules are available in HDPE bottles or blister packs, depending on the market. Each package includes a patient information leaflet with detailed usage instructions.

Manufacturer

Atazanavir Krka is manufactured by KRKA, d.d., Novo mesto, Slovenia. KRKA is a major European pharmaceutical company specializing in the development and production of high-quality generic medicines. The marketing authorization is held by KRKA, d.d., Novo mesto. The medicine is manufactured in accordance with Good Manufacturing Practice (GMP) standards as required by the European Medicines Agency.