Raltegravir Zentiva 600 mg
Generic HIV Integrase Strand Transfer Inhibitor for Once-Daily Antiretroviral Therapy
Quick Facts About Raltegravir Zentiva
Key Takeaways
- Raltegravir Zentiva 600 mg is a generic version of raltegravir, an HIV integrase strand transfer inhibitor (INSTI) that prevents the virus from inserting its DNA into human cells, helping to reduce viral load and improve CD4 cell counts.
- The standard dose in adults and adolescents (aged 12 years and weighing at least 40 kg) is two 600 mg tablets (1200 mg) taken once daily, with or without food, always in combination with other antiretroviral medicines.
- Raltegravir Zentiva does not cure HIV – patients must continue their full antiretroviral regimen without interruption to maintain viral suppression and avoid developing drug resistance.
- Aluminium-, magnesium- and calcium-containing antacids can significantly reduce the effectiveness of the 600 mg formulation and should not be co-administered; iron and other polyvalent cation supplements must be separated by at least 2 hours.
- Serious adverse reactions are uncommon but include severe skin reactions (Stevens-Johnson syndrome, DRESS), depression with suicidal ideation, rhabdomyolysis, hepatotoxicity and immune reconstitution inflammatory syndrome – any severe symptoms warrant urgent medical attention.
What Is Raltegravir Zentiva and What Is It Used For?
Raltegravir Zentiva is a generic antiretroviral medicine authorised in the European Economic Area (EEA) and in other jurisdictions that recognise generic approval pathways based on bioequivalence. It contains the active substance raltegravir as potassium salt, an HIV-1 integrase strand transfer inhibitor originally developed by Merck Sharp & Dohme and marketed as Isentress. Following expiry of key patents and supplementary protection certificates covering the 400 mg formulation, generic manufacturers such as Zentiva k.s. have been able to produce bioequivalent versions of raltegravir at reduced cost, supporting wider access to integrase inhibitor-based antiretroviral therapy (ART).
HIV-1 is a retrovirus that primarily targets CD4+ T lymphocytes, the white blood cells that coordinate the body’s defence against infections. If untreated, chronic HIV-1 infection progressively depletes CD4 cells, eventually resulting in acquired immunodeficiency syndrome (AIDS), characterised by severe immune compromise, opportunistic infections and certain cancers. Modern antiretroviral therapy aims to suppress viral replication to below the limits of detection of clinical assays (typically <50 copies/mL or <20 copies/mL), preserve or restore immune function, reduce AIDS-related morbidity and mortality, and eliminate sexual transmission of HIV through the undetectable = untransmittable (U=U) principle.
Raltegravir was the first approved member of the INSTI class, receiving US Food and Drug Administration (FDA) approval in 2007 and European Medicines Agency (EMA) approval in 2008. The introduction of integrase inhibitors was a pivotal advance in HIV therapeutics because it provided a potent new mechanism of action distinct from the existing nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs). The 600 mg high-dose formulation was developed to enable once-daily administration and was authorised in Europe and the United States in 2017, following the pivotal ONCEMRK clinical trial demonstrating non-inferiority to the 400 mg twice-daily regimen.
Mechanism of Action
Raltegravir selectively inhibits HIV-1 integrase, one of three essential viral enzymes required for HIV replication alongside reverse transcriptase and protease. The HIV life cycle begins when the virus attaches to CD4 receptors and co-receptors (CCR5 or CXCR4) on host cells, fuses its lipid envelope with the cell membrane, and releases its genetic material (single-stranded RNA) and enzymes into the cytoplasm. Reverse transcriptase converts the viral RNA into double-stranded proviral DNA. Integrase then transports this DNA into the cell nucleus and catalyses its insertion into host chromosomal DNA through a two-step process: 3′-processing (trimming of DNA ends) and strand transfer (covalent insertion into host DNA).
Raltegravir blocks the strand transfer step, forming a chelating interaction with the divalent magnesium cations at the active site of integrase. By preventing integration, raltegravir halts productive viral replication and limits the accumulation of HIV DNA in the host genome. The drug is highly selective for HIV integrase and does not affect host cellular enzymes, contributing to its generally favourable tolerability profile. Because the integrase enzyme is unique to retroviruses and has no human equivalent, INSTIs have a low potential for off-target effects compared with drug classes targeting host cellular functions.
Clinical Indications
Raltegravir Zentiva 600 mg is indicated, in combination with other antiretroviral medicinal products, for the treatment of HIV-1 infection in adults, adolescents and children weighing at least 40 kg. It may be used in both treatment-naive patients (those starting antiretroviral therapy for the first time) and in treatment-experienced virologically suppressed patients (those already on a stable raltegravir 400 mg twice-daily regimen who wish to simplify to once-daily dosing). According to current US Department of Health and Human Services (DHHS) and European AIDS Clinical Society (EACS) guidelines, raltegravir remains a recommended INSTI option, though newer second-generation INSTIs (dolutegravir, bictegravir) are generally preferred for initial therapy because of their higher genetic barrier to resistance.
Raltegravir continues to have specific roles in clinical practice: as a component of post-exposure prophylaxis (PEP) regimens, in patients with drug interactions that preclude dolutegravir or bictegravir, and as an alternative first-line option in pregnancy where extensive safety data exist. The DHHS Perinatal HIV Guidelines list raltegravir as a preferred INSTI for pregnant women needing rapid viral suppression, although the 600 mg once-daily formulation specifically is not recommended during pregnancy due to insufficient pharmacokinetic data.
It is essential to recognise that Raltegravir Zentiva does not cure HIV infection. Even when viral load is suppressed to undetectable levels for many years, the virus persists in latent reservoirs within resting memory CD4 cells, anatomical sanctuaries such as the central nervous system, and other tissue compartments. Patients must continue taking their complete antiretroviral regimen consistently to maintain viral suppression, preserve immune function and prevent the emergence of drug resistance. Raltegravir is never used as monotherapy: single-drug use of any antiretroviral leads rapidly to selection of resistant viral variants.
What Should You Know Before Taking Raltegravir Zentiva?
Contraindications
Raltegravir Zentiva is contraindicated in patients with known hypersensitivity to raltegravir or to any of the excipients listed in the composition section. Although true hypersensitivity reactions are rare, severe and potentially life-threatening events including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS) have been reported in post-marketing surveillance. If a hypersensitivity reaction is suspected, Raltegravir Zentiva should be discontinued immediately and appropriate medical treatment started – delay in discontinuing raltegravir after the onset of severe rash or hypersensitivity reactions may result in a life-threatening reaction.
Warnings and Precautions
Before initiating Raltegravir Zentiva, patients should discuss their complete medical, psychiatric, and medication history with their healthcare provider. Several important warnings and precautions apply to the use of this medicine, and these are discussed in detail below.
Mental health and depression: Depression, including suicidal ideation and suicidal behaviour, has been reported in patients receiving raltegravir, particularly those with a pre-existing history of psychiatric illness. Patients, carers and clinicians should be vigilant for any changes in mood, increased feelings of hopelessness, withdrawal, or unusual behavioural changes, and should report these promptly. The risk-benefit assessment should be carefully considered in patients with a history of depression, bipolar disorder, schizophrenia or prior suicide attempts, and such patients may require additional monitoring. Regular screening using validated instruments such as the Patient Health Questionnaire (PHQ-9) may be appropriate in high-risk individuals.
Severe skin and hypersensitivity reactions: Severe, potentially life-threatening, and in some cases fatal cutaneous reactions – including SJS, TEN and DRESS – have been reported with raltegravir. These reactions may include fever, blisters, mucosal involvement (oral, ocular or genital), eosinophilia, hepatitis, nephritis, angioedema, and multi-organ dysfunction. Patients developing a rash associated with any of these features should stop Raltegravir Zentiva immediately and seek urgent medical evaluation. Hypersensitivity reactions have been reported in patients receiving concomitant medicines known to cause such reactions; when Raltegravir Zentiva is discontinued because of a suspected hypersensitivity reaction, other suspected causative agents should also be discontinued.
Hepatotoxicity: Cases of hepatitis, hepatic failure and elevated liver enzymes (aminotransferases, alkaline phosphatase, bilirubin) have been reported in patients treated with raltegravir, including some with underlying hepatic disease or co-infection with hepatitis B virus (HBV) or hepatitis C virus (HCV). A causal relationship has not always been established, but patients with pre-existing hepatic impairment or viral hepatitis should be monitored closely. Baseline liver function tests and periodic monitoring during therapy are recommended, with dose interruption or discontinuation considered in cases of significant hepatic dysfunction.
Rhabdomyolysis and myopathy: Rhabdomyolysis (severe muscle breakdown with release of muscle cell contents into the blood) and myopathy have been reported in patients taking raltegravir. Patients should seek medical attention promptly if they develop unexplained muscle pain, tenderness, weakness, dark urine (suggesting myoglobinuria) or symptoms of acute kidney injury. Creatine kinase (CK) levels should be measured when clinically indicated. Raltegravir should be used with caution in patients with a history of myopathy, elevated CK or in those receiving concomitant medicines known to cause these effects (for example, statins, fibrates or certain antibiotics).
Immune reconstitution inflammatory syndrome (IRIS): In HIV-infected patients with severe immune deficiency at the time of initiating ART, an inflammatory reaction to previously subclinical or residual opportunistic infections may occur shortly after starting therapy, causing clinical deterioration. Typical examples include paradoxical worsening of tuberculosis, cytomegalovirus retinitis, Pneumocystis jirovecii pneumonia, cryptococcal meningitis and Mycobacterium avium complex disease. Autoimmune disorders (such as Graves’ disease, autoimmune hepatitis, polymyositis, and Guillain-Barré syndrome) have also been reported to occur in the setting of immune reconstitution, sometimes months after initiation of ART. Any suggestive symptoms should be evaluated and treated as clinically appropriate.
Osteonecrosis: Although the aetiology is multifactorial (including corticosteroid use, alcohol consumption, severe immunosuppression, high body mass index, advanced HIV disease and prolonged combination ART), cases of osteonecrosis have been reported, particularly in patients with advanced HIV disease and/or long-term exposure to combination antiretroviral therapy. Patients should seek medical advice if they experience joint aches and pain, joint stiffness, or difficulty in movement, especially affecting the hip, knee or shoulder.
Pregnancy and Breastfeeding
Raltegravir has been studied extensively in pregnancy, and observational data from the Antiretroviral Pregnancy Registry, the US DHHS cohorts and the European Pregnancy and Paediatric HIV Cohort Collaboration have been generally reassuring regarding major congenital anomalies and preterm birth. International perinatal HIV guidelines therefore include raltegravir as a recommended or alternative INSTI option during pregnancy. Importantly, however, the 600 mg once-daily formulation (including Raltegravir Zentiva 600 mg) is not recommended during pregnancy because pharmacokinetic studies show reduced drug exposure in pregnant women – particularly during the third trimester – and there is a theoretical risk of insufficient viral suppression. Pregnant women requiring raltegravir should receive the 400 mg twice-daily formulation instead.
Breastfeeding is not recommended for women living with HIV in resource-rich settings where safe and effective replacement feeding is available, because HIV can be transmitted to the infant through breast milk. In settings where replacement feeding is not feasible, the WHO recommends continued breastfeeding combined with ART for the mother and postnatal prophylaxis for the infant to minimise transmission risk. The decision to breastfeed while taking Raltegravir Zentiva should be made in consultation with a specialist HIV clinician and based on individual circumstances, local guidelines and the availability of safe alternatives.
Driving and Operating Machinery
Dizziness has been reported in some patients treated with raltegravir and may affect the ability to drive and use machines. Patients who experience dizziness, somnolence or other central nervous system effects should avoid driving, operating heavy machinery or engaging in activities that require full alertness until they know how the medicine affects them.
Renal and Hepatic Impairment
No dose adjustment of Raltegravir Zentiva is required in patients with mild or moderate renal impairment. Data in patients with severe renal impairment or end-stage renal disease (ESRD) requiring dialysis are limited; the drug is unlikely to be significantly removed by haemodialysis due to its high protein binding. Caution and clinical monitoring are advised in this population.
No dose adjustment is required in patients with mild to moderate hepatic impairment (Child-Pugh Class A or B). Raltegravir Zentiva has not been studied in patients with severe hepatic impairment (Child-Pugh Class C) and is therefore not recommended in these patients. Close monitoring is advised in patients with known or suspected underlying liver disease, including HBV or HCV co-infection.
How Does Raltegravir Zentiva Interact with Other Drugs?
Understanding drug interactions is crucial for safe and effective use of Raltegravir Zentiva. Raltegravir is metabolised primarily by uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) through glucuronidation, with only a minor contribution from the cytochrome P450 (CYP450) enzyme system. This relatively ‘clean’ metabolic profile means raltegravir has fewer interactions than many other antiretrovirals (especially those metabolised by or inducing CYP3A4). Nevertheless, several clinically important interactions exist, particularly with inducers of UGT1A1 and with products containing polyvalent metal cations.
The 600 mg formulation is more sensitive to certain interactions than the 400 mg formulation because of differences in its pharmacokinetic profile: lower area under the concentration-time curve (AUC) relative to trough concentrations, and a more pronounced effect of co-administered polyvalent cations on absorption. Consequently, some interactions that are manageable with dose separation in the 400 mg formulation are best avoided entirely with the 600 mg formulation.
| Interacting Drug or Class | Effect | Recommendation |
|---|---|---|
| Rifampicin | Strong UGT1A1 inducer; markedly reduces raltegravir plasma levels | Co-administration with Raltegravir Zentiva 600 mg is not recommended. If required, switch to raltegravir 400 mg twice daily with dose doubling. |
| Rifabutin | Moderate UGT1A1 induction; smaller effect than rifampicin | Use with caution; the 400 mg twice-daily formulation may be preferred. |
| Aluminium/Magnesium antacids | Chelation of raltegravir, markedly reduced absorption | Co-administration not recommended with the 600 mg formulation, regardless of dosing interval. |
| Calcium carbonate antacids | Reduces raltegravir absorption (larger effect with 600 mg formulation) | Co-administration not recommended with the 600 mg formulation. |
| Iron supplements, multivitamins with polyvalent cations | May reduce raltegravir absorption through chelation | Separate by at least 2 hours before or 6 hours after Raltegravir Zentiva 600 mg. |
| Proton pump inhibitors (PPIs), H2-receptor antagonists | Increase raltegravir plasma levels (variable magnitude) | No dose adjustment usually required; may be used when acid suppression is needed. |
| Atazanavir (± ritonavir) | Increases raltegravir plasma levels via UGT1A1 inhibition | Generally safe; no dose adjustment required. Monitor for adverse effects. |
| Tipranavir/ritonavir | Decreases raltegravir plasma levels | Co-administration with Raltegravir Zentiva 600 mg is not recommended. |
| Etravirine | Induces UGT1A1, decreases raltegravir exposure | Co-administration with Raltegravir Zentiva 600 mg is not recommended. |
| Carbamazepine, Phenytoin, Phenobarbital | Strong UGT1A1/CYP inducers; reduce raltegravir exposure | Avoid with Raltegravir Zentiva 600 mg; consider alternative anticonvulsants such as valproate or lamotrigine. |
| St. John’s Wort (Hypericum perforatum) | Herbal UGT/CYP inducer; reduces raltegravir levels | Avoid concomitant use. |
| Methadone, Oral contraceptives, Statins | No clinically significant interaction with raltegravir | No dose adjustment required. |
Major Interactions
Rifampicin is the most clinically important inducer of UGT1A1 and substantially reduces raltegravir plasma concentrations. Because rifampicin is central to first-line tuberculosis (TB) treatment – a leading co-infection in people living with HIV, particularly in sub-Saharan Africa and South-East Asia – this interaction has major public health implications. For patients on rifampicin, the 600 mg once-daily formulation is not recommended; instead, raltegravir 400 mg should be used at a doubled dose of 800 mg twice daily, or an alternative antiretroviral should be selected. Dolutegravir 50 mg twice daily is an established alternative in patients receiving rifampicin.
Antacids containing polyvalent metal cations (aluminium, magnesium, calcium) significantly reduce raltegravir absorption through chelation. While the 400 mg formulation can sometimes be managed by separating dosing by several hours, studies of the 600 mg formulation show that polyvalent cation antacids substantially reduce drug exposure even when administered hours apart. For this reason, concomitant use of aluminium/magnesium antacids and calcium carbonate antacids is not recommended with Raltegravir Zentiva 600 mg. Patients requiring acid suppression should be offered proton pump inhibitors (omeprazole, pantoprazole, esomeprazole) or H2-receptor antagonists (famotidine), which do not reduce raltegravir absorption.
Etravirine, a second-generation NNRTI, is a moderate UGT1A1 inducer and decreases raltegravir exposure. Clinical data indicate that this interaction is manageable with the 400 mg twice-daily formulation but may compromise efficacy with the 600 mg once-daily regimen. Raltegravir Zentiva 600 mg should therefore not be co-administered with etravirine; the 400 mg formulation may be used where clinically appropriate.
Minor Interactions
Iron supplements, multivitamins with iron or calcium, and certain mineral supplements may reduce raltegravir absorption via chelation of divalent cations. Patients taking iron supplements (for example, for iron-deficiency anaemia or during pregnancy) should separate them from Raltegravir Zentiva 600 mg by at least 2 hours before or 6 hours after dosing. Calcium supplements should be similarly separated, and patients should discuss the overall schedule with their pharmacist.
Atazanavir, an HIV protease inhibitor that inhibits UGT1A1, increases raltegravir plasma levels when co-administered. In clinical trials, atazanavir/ritonavir increased raltegravir AUC by approximately 41–72%. Despite this increase, raltegravir has a wide therapeutic index and no dose adjustment is required; clinicians should, however, monitor for potential adverse effects such as gastrointestinal intolerance or CNS symptoms.
Methadone, oral hormonal contraceptives, statins (atorvastatin, rosuvastatin), and most SSRIs have not shown clinically significant interactions with raltegravir and may generally be co-administered without dose adjustment, subject to clinical monitoring.
What Is the Correct Dosage of Raltegravir Zentiva?
Raltegravir Zentiva must always be used exactly as prescribed by the healthcare provider and always as part of a complete antiretroviral regimen. Proper administration is essential to maintain therapeutic drug concentrations, ensure sustained viral suppression and minimise the risk of emergent drug resistance. The dosage recommendations below are aligned with the Summary of Product Characteristics (SmPC) for Raltegravir Zentiva 600 mg and with international HIV treatment guidelines.
Adults
Adult Dosage (weight ≥ 40 kg)
The recommended dose is two 600 mg tablets (total 1200 mg) taken orally once daily. Tablets should be swallowed whole with a glass of water and not chewed, crushed or split, as this may alter the pharmacokinetic profile of the drug. Raltegravir Zentiva 600 mg can be taken with or without food.
The once-daily regimen is supported by the pivotal ONCEMRK study, a phase III non-inferiority trial in treatment-naive adults which demonstrated that raltegravir 1200 mg once daily (two 600 mg tablets) achieved virological suppression rates comparable to raltegravir 400 mg twice daily at 48 and 96 weeks. Long-term follow-up confirmed durable efficacy and a safety profile consistent with the established 400 mg formulation, providing a convenient once-daily option that can enhance adherence, particularly for patients new to antiretroviral therapy.
Adherence is the most important determinant of long-term antiretroviral success. Patients should take Raltegravir Zentiva at approximately the same time each day and establish a dosing routine linked to an existing habit (such as a daily meal or bedtime). Missed doses should be handled according to the guidance in the Missed Dose section below, and patients should never share medicines, reduce or increase doses on their own, or stop treatment without first consulting their healthcare provider.
Adolescents and Children
Adolescents and Children (≥ 12 years and weight ≥ 40 kg)
The recommended dose is two 600 mg tablets (total 1200 mg) taken orally once daily, the same as the adult dose. This regimen applies to adolescents aged 12 years and older weighing at least 40 kg who are treatment-naive or who are virologically suppressed on a stable raltegravir 400 mg twice-daily regimen.
For children weighing less than 40 kg, or for younger children unable to swallow 600 mg tablets, alternative raltegravir formulations (chewable tablets, granules for oral suspension) with weight-based dosing should be used. These weight-based dosing schedules are detailed in the 400 mg and paediatric formulations’ SmPC. The choice of formulation and dose should be determined by the prescribing paediatric HIV specialist based on the child’s weight, ability to swallow tablets, treatment history and overall regimen.
Elderly Patients
Elderly Dosage (≥ 65 years)
There is no specific dose adjustment required for elderly patients. However, clinical experience with Raltegravir Zentiva in patients over 65 years of age is limited. Caution is advised because of the greater frequency of co-morbidities, polypharmacy, and reduced hepatic or renal function in this population.
Older adults living with HIV are an expanding population thanks to the success of modern ART. Polypharmacy, age-related organ function changes, drug-drug-disease interactions and increased risk of adverse events make individualised assessment particularly important. Clinicians should perform regular medication reviews, monitor for potential interactions (especially with newly added medicines), and assess bone health, renal function, cardiovascular risk and mental health at each visit.
Renal Impairment
Renal Impairment
No dose adjustment is required in patients with mild or moderate renal impairment. Data in patients with severe renal impairment or end-stage renal disease are limited – caution is advised.
Hepatic Impairment
Hepatic Impairment
No dose adjustment is required in patients with mild to moderate hepatic impairment (Child-Pugh A or B). Raltegravir Zentiva has not been studied in patients with severe hepatic impairment (Child-Pugh C) and is therefore not recommended in these patients.
Missed Dose
If a dose is missed and it is remembered within a few hours of the scheduled time, take the missed dose as soon as possible and continue with the next scheduled dose. If it is almost time for the next dose, skip the missed dose and continue with the regular schedule. Do not take a double dose to compensate for a missed dose. For a medicine that is taken once daily, missing a dose means that the interval to the next dose is longer than 24 hours, so prompt action is particularly important. Patients who frequently forget doses should discuss practical adherence aids (pill organisers, phone alarms, adherence apps) with their healthcare team.
Overdose
There is limited clinical experience with raltegravir overdose. No specific antidote exists. In the event of an overdose, general supportive measures should be instituted, including monitoring of vital signs, observation of clinical status, and standard supportive care such as maintenance of a clear airway, adequate hydration, and treatment of any arising complications. Because raltegravir is highly bound to plasma proteins (approximately 83%), it is unlikely to be significantly removed by haemodialysis. If an overdose is suspected, contact the local poison control centre or the emergency department for guidance and further management.
What Are the Side Effects of Raltegravir Zentiva?
Like all medicines, Raltegravir Zentiva may cause side effects, although not everyone who takes it will experience them. Most adverse reactions associated with raltegravir are mild to moderate and tend to improve or resolve as the body adjusts to treatment. However, some reactions can be severe and require prompt medical attention. The frequency categories used here are based on pooled data from pivotal clinical trials (STARTMRK, BENCHMRK, ONCEMRK) and post-marketing surveillance, classified according to the European Medicines Agency convention.
The 600 mg once-daily formulation showed a safety profile comparable to the 400 mg twice-daily regimen in the ONCEMRK trial, with generally similar rates of treatment-related adverse events. Discontinuation rates due to adverse events remained low in both arms, consistent with the class tolerability of integrase inhibitors.
Common Side Effects
May affect up to 1 in 10 people (≥ 1%, < 10%)
- Decreased appetite
- Difficulty sleeping (insomnia), abnormal dreams, nightmares
- Behavioural changes, feelings of deep sadness and worthlessness (depression)
- Dizziness, headache
- Vertigo (spinning sensation)
- Abdominal pain, bloating, diarrhoea, excessive gas (flatulence), nausea, vomiting
- Indigestion (dyspepsia), belching
- Various types of rash (more frequent when combined with darunavir)
- Tiredness, unusual fatigue or weakness, fever
- Elevated liver enzymes (ALT, AST)
- Abnormal white blood cell counts in blood tests
- Elevated blood lipids (cholesterol, triglycerides), elevated pancreatic/salivary enzymes
Uncommon Side Effects
May affect up to 1 in 100 people (≥ 0.1%, < 1%)
- Herpes simplex infections, herpes zoster (shingles)
- Anaemia, including iron-deficiency anaemia
- Signs and symptoms of infection or inflammation
- Mental health disorders, suicidal ideation or attempted suicide
- Anxiety, confusion, mood changes, panic attacks
- Memory loss, attention deficit, taste changes (dysgeusia), increased drowsiness
- Migraine, peripheral neuropathy, paraesthesia, tremor
- Visual disturbances, tinnitus (ringing in the ears)
- Palpitations, bradycardia, tachycardia, arrhythmias
- Hot flushes, elevated blood pressure
- Dysphonia (hoarseness), nosebleeds, nasal congestion
- Gastritis, hepatitis, liver failure, hepatic steatosis
- Constipation, dry mouth, heartburn, pancreatitis
- Acne, unusual hair loss (alopecia), skin redness, excessive sweating, night sweats
- Allergic rash, angio-oedema
- Joint pain, back pain, bone pain, muscle weakness, neck pain
- Acute kidney injury, nephrolithiasis (kidney stones), tubulo-interstitial nephritis, nocturia
- Erectile dysfunction, breast enlargement in males (gynaecomastia), menopausal symptoms
- Chest discomfort, chills, facial swelling, general malaise
- Neutropenia, thrombocytopenia
- Increased creatinine, weight gain, lipodystrophy
- Hyperglycaemia, diabetes mellitus, excessive thirst
- Upper respiratory tract infection, folliculitis, warts, lymphadenopathy
Serious Adverse Reactions (Rare but Severe)
Seek immediate medical attention
- Severe cutaneous adverse reactions: Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN)
- Drug reaction with eosinophilia and systemic symptoms (DRESS)
- Severe hypersensitivity reactions with multi-organ involvement
- Rhabdomyolysis with severe muscle pain, dark urine or acute kidney injury
- Liver failure with jaundice
- Suicidal behaviour (including completed suicide)
- Cerebellar ataxia
- Immune reconstitution inflammatory syndrome (IRIS)
- Autoimmune disorders (Guillain-Barré syndrome, Graves’ disease, autoimmune hepatitis, polymyositis)
- Osteonecrosis (avascular necrosis of bone)
Additional Considerations in Adolescents
In paediatric and adolescent clinical trials of raltegravir (such as IMPAACT P1066 and the paediatric arm of ONCEMRK), hyperactivity has been reported as an additional common adverse event not typically seen in adults. Otherwise, the safety profile observed in adolescents aged 12 years and older weighing at least 40 kg (the population for whom the 600 mg formulation is approved) is generally consistent with adults. Healthcare providers should monitor adolescents for both somatic adverse reactions and age-specific behavioural, school-performance and developmental effects.
Immune Reconstitution Inflammatory Syndrome
In patients with advanced HIV infection and severely compromised immune systems (CD4 count below 200 cells/mm3, particularly below 50 cells/mm3), the initiation of combination antiretroviral therapy – including regimens containing Raltegravir Zentiva – can trigger IRIS. As the immune system rapidly recovers, it may mount exaggerated inflammatory responses to previously subclinical or treated opportunistic infections. Typical triggers include Mycobacterium avium complex disease, tuberculosis, cytomegalovirus retinitis, Pneumocystis jirovecii pneumonia and cryptococcal meningitis. IRIS usually occurs within the first few weeks to months of ART initiation and responds to continued ART, appropriate treatment of the underlying opportunistic pathogen, and in selected severe cases, corticosteroids.
Body Weight and Metabolic Changes
Weight gain has been reported with all modern antiretroviral regimens, including those containing integrase inhibitors such as raltegravir. Although the magnitude of weight gain with raltegravir appears to be modest compared with some second-generation INSTIs, patients – particularly women, Black patients, and those starting with a low baseline body mass index or low CD4 count – may experience weight increase, which can have cardiometabolic implications. Lifestyle counselling, nutritional support and monitoring of lipid and glucose parameters are recommended.
How Should You Store Raltegravir Zentiva?
Proper storage of Raltegravir Zentiva is essential to maintain the stability, potency and efficacy of the medicine throughout its shelf life. Patients should read the storage instructions on the outer carton and in the patient information leaflet supplied with the pack, as specific temperature limits and packaging descriptions may vary slightly between countries and pack sizes.
- Temperature: Store in the original packaging. Check the outer carton and patient information leaflet for specific temperature requirements; the 600 mg formulation typically does not require refrigeration and may be stored at room temperature (below 30 °C).
- Moisture protection: Keep the bottle tightly closed to protect from moisture. If the tablets are supplied in blister packs, do not remove them until ready to take.
- Light protection: Store in the original packaging to protect from light.
- Desiccant: If a desiccant sachet is included in the bottle, do not remove, swallow or discard it – it protects the tablets from moisture.
- Child safety: Keep this medicine out of the sight and reach of children. Use child-resistant closures and consider storing in a locked cabinet if children or vulnerable adults have access to the home.
- Expiry date: Do not use after the expiry date (marked “EXP”) stated on the packaging. The expiry date refers to the last day of that month.
- Disposal: Do not dispose of medicines via wastewater or household waste. Return unused or expired Raltegravir Zentiva to a pharmacy or a local medicines disposal programme to protect the environment.
What Does Raltegravir Zentiva Contain?
Understanding the composition of Raltegravir Zentiva is important for patients with known allergies or intolerances to specific excipients. Generic medicinal products are bioequivalent to the reference product but may contain different excipients. Patients switching from the originator product to Raltegravir Zentiva (or between different generics) should review the list of excipients in the supplied leaflet to identify any that they may be intolerant to. The table below lists the typical components of the 600 mg film-coated tablet formulation; always refer to the current patient information leaflet for the definitive composition.
| Component | Function |
|---|---|
| Raltegravir (as potassium salt) – 600 mg | Active substance (HIV integrase strand transfer inhibitor) |
| Microcrystalline cellulose | Filler/binder |
| Hypromellose | Binder / controlled-release polymer |
| Croscarmellose sodium | Disintegrant |
| Lactose monohydrate | Diluent |
| Magnesium stearate | Lubricant |
| Colloidal anhydrous silica | Glidant |
| Polyvinyl alcohol, titanium dioxide, polyethylene glycol, talc, colourants | Film-coating components (aesthetic, protective) |
Appearance and Packaging
Raltegravir Zentiva 600 mg film-coated tablets are typically oval in shape with distinctive colouring and markings defined by the manufacturer to aid identification. The tablets are supplied in high-density polyethylene (HDPE) bottles or in blister packs made of aluminium or PVC/aluminium, typically in pack sizes containing 60 tablets (a one-month supply at two tablets daily). Specific pack presentations, tablet appearance and debossings may vary by country and may not all be marketed in every jurisdiction.
Bioequivalence and Generic Substitution
As a generic medicine, Raltegravir Zentiva 600 mg has been authorised on the basis of demonstrated bioequivalence to the reference medicinal product (Isentress 600 mg film-coated tablets). Bioequivalence studies performed in healthy volunteers have shown that the pharmacokinetic parameters (maximum plasma concentration, Cmax; and area under the concentration-time curve, AUC) of Raltegravir Zentiva fall within the internationally accepted bioequivalence limits of 80–125% compared with the reference product. Patients can therefore expect Raltegravir Zentiva 600 mg to provide comparable efficacy and safety to the originator, while potentially offering improved affordability and health-system sustainability.
Frequently Asked Questions About Raltegravir Zentiva
Raltegravir Zentiva is a generic medicine used, in combination with other antiretroviral medicines, to treat HIV-1 infection in adults and adolescents aged 12 years and weighing at least 40 kg. It belongs to the integrase strand transfer inhibitor (INSTI) class and works by blocking the HIV integrase enzyme, preventing the virus from inserting its genetic material into human cells. The 600 mg formulation is designed for once-daily administration (two tablets, total 1200 mg). Raltegravir Zentiva is always used as part of a complete antiretroviral regimen and does not cure HIV.
Raltegravir Zentiva is a generic version of the reference medicinal product Isentress 600 mg, produced by Zentiva k.s. It contains the same active substance (raltegravir, as potassium salt), the same strength (600 mg), and the same pharmaceutical form (film-coated tablet). Generic medicines are authorised only after demonstrating bioequivalence to the reference product in pharmacokinetic studies and must meet the same quality and manufacturing standards. You can therefore expect Raltegravir Zentiva to provide comparable efficacy, safety and tolerability to Isentress. Excipients (inactive ingredients) may differ, so patients with specific excipient intolerances should check the patient information leaflet.
The recommended dose in adults and adolescents weighing at least 40 kg is two 600 mg tablets (total 1200 mg) taken by mouth once daily, with or without food. The tablets must be swallowed whole with water; do not chew, crush or split them. Raltegravir Zentiva must always be used in combination with other antiretroviral medicines prescribed by your doctor. Try to take the medicine at the same time each day to establish a consistent routine, and always complete your full prescribed regimen without interruption.
Aluminium- and magnesium-containing antacids and calcium carbonate antacids should not be taken with Raltegravir Zentiva 600 mg because they significantly reduce raltegravir absorption through chelation. If acid suppression is needed, your doctor can recommend alternatives such as proton pump inhibitors (omeprazole, pantoprazole) or H2-receptor antagonists (famotidine), which do not significantly interact with raltegravir. Iron supplements, calcium supplements and multivitamins containing polyvalent cations should be separated from Raltegravir Zentiva by at least 2 hours before or 6 hours after dosing. Always discuss all medicines and supplements with your healthcare provider or pharmacist.
The most common side effects are headache, insomnia (difficulty sleeping), abnormal dreams, dizziness, nausea, diarrhoea, abdominal pain, fatigue and rash. Elevated liver enzymes, blood lipids and amylase/lipase may also be detected in laboratory tests. Most of these effects are mild to moderate and improve over the first few weeks of treatment. Less common but more serious reactions include depression with suicidal thoughts, severe skin reactions (Stevens-Johnson syndrome, DRESS), rhabdomyolysis, liver problems and immune reconstitution inflammatory syndrome (IRIS). Contact your healthcare provider promptly if any side effect becomes severe, persistent or worrying.
Raltegravir has extensive safety data in pregnancy, and international HIV guidelines (DHHS, BHIVA, EACS) include it as a recommended INSTI option during pregnancy. However, the 600 mg once-daily formulation specifically (including Raltegravir Zentiva 600 mg) is not recommended during pregnancy because of reduced drug exposure observed in pharmacokinetic studies in pregnant women. Pregnant women needing raltegravir should use the 400 mg twice-daily formulation instead. Breastfeeding is generally not recommended for women living with HIV in settings where safe alternative feeding is available, because HIV can be transmitted to the infant through breast milk. Women who are pregnant, planning pregnancy or breastfeeding should discuss their treatment plan with an HIV specialist.
If you miss a dose, take it as soon as you remember. If it is almost time for your next dose, skip the missed dose and continue with your normal schedule. Never take a double dose to make up for a missed one. Because Raltegravir Zentiva 600 mg is taken once daily, missing a dose is more likely to create a meaningful gap in drug coverage than a twice-daily regimen; consistent daily dosing is essential to maintain viral suppression and avoid the development of drug resistance. Use adherence aids such as pill organisers, smartphone alarms or HIV-specific apps if you often forget doses, and discuss adherence challenges openly with your HIV clinic team.
References
This article is based on peer-reviewed medical literature, regulatory documents and international clinical practice guidelines. All medical claims are supported by evidence level 1A (systematic reviews and meta-analyses of randomised controlled trials) where available.
- European Medicines Agency (EMA). Raltegravir Zentiva – European Public Assessment Report (EPAR) and Summary of Product Characteristics. Available at: www.ema.europa.eu/en/medicines.
- European Medicines Agency (EMA). Isentress – Summary of Product Characteristics (reference medicinal product). Merck Sharp & Dohme B.V.
- U.S. Food and Drug Administration (FDA). Isentress HD (raltegravir) 600 mg Prescribing Information. Merck Sharp & Dohme Corp.
- World Health Organization (WHO). Consolidated Guidelines on HIV Prevention, Testing, Treatment, Service Delivery and Monitoring: Recommendations for a Public Health Approach. Geneva: WHO; 2021.
- Panel on Antiretroviral Guidelines for Adults and Adolescents (DHHS). Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents with HIV. Department of Health and Human Services. Updated 2024.
- Panel on Treatment of Pregnant Women with HIV Infection and Prevention of Perinatal Transmission (DHHS). Recommendations for the Use of Antiretroviral Drugs in Pregnant Women with HIV Infection. Updated 2024.
- European AIDS Clinical Society (EACS). EACS Guidelines, Version 12.0, October 2023. Available at: www.eacsociety.org/guidelines.
- British HIV Association (BHIVA). Guidelines for the Treatment of HIV-1-Positive Adults with Antiretroviral Therapy. 2023.
- Cahn P, Kaplan R, Sax PE, et al. Raltegravir 1200 mg once daily versus raltegravir 400 mg twice daily, with tenofovir disoproxil fumarate and emtricitabine, for previously untreated HIV-1 infection: a randomised, double-blind, parallel-group, phase 3, non-inferiority trial (ONCEMRK). Lancet HIV. 2017;4(11):e486–e494.
- Lennox JL, DeJesus E, Rockstroh JK, et al. Long-term efficacy and safety of raltegravir-based therapy in treatment-naïve patients: 5-year results of the STARTMRK study. J Acquir Immune Defic Syndr. 2014;65(4):453–462.
- Steigbigel RT, Cooper DA, Teppler H, et al. Long-term efficacy and safety of raltegravir combined with optimized background therapy in treatment-experienced patients with drug-resistant HIV infection: BENCHMRK combined 156-week results. Clin Infect Dis. 2010;50(4):605–612.
- Nachega JB, Parienti JJ, Uthman OA, et al. Lower pill burden and once-daily antiretroviral treatment regimens for HIV infection: A meta-analysis of randomized controlled trials. Clin Infect Dis. 2014;58(9):1297–1307.
- British National Formulary (BNF). Raltegravir. Available at: bnf.nice.org.uk.
Editorial Team
This article has been written and reviewed by the iMedic Medical Editorial Team, comprising licensed physicians with specialisation in infectious disease, virology and clinical pharmacology. Our editorial process follows strict evidence-based principles and the GRADE framework for evidence appraisal.
iMedic Medical Editorial Team – specialists in infectious disease, HIV medicine and clinical pharmacology with documented academic backgrounds and clinical experience.
iMedic Medical Review Board – independent panel of medical experts who review all content according to international guidelines (WHO, DHHS, EACS, BHIVA) and the GRADE evidence framework.
Last medical review: . Next scheduled review: . All content is reviewed at least every 6 months to ensure accuracy and alignment with the latest clinical evidence.