Pronunciation(s): KRIK-sih-van; in-DIH-nuh-veer
|What is Crixivan?
- Crixivan is an anti-HIV medication. It is in a category of HIV medications called protease inhibitors (PIs). Crixivan prevents T-cells that have been infected with HIV from producing new HIV.
- Crixivan, manufactured by Merck & Company, was approved for the treatment of HIV by the U.S. Food and Drug Administration (FDA) in 1996.
- Crixivan must be used in combination with at least two other anti-HIV drugs.
- Merck has established a patient assistance program (PAP) for people living with HIV who do not have private or public health insurance and are unable to afford Crixivan. To learn more about the PAP for Isentress, call 800-850-3430.
What is known about Crixivan?
- Crixivan can be taken either three times a day or twice a day:
- The three-times-daily Crixivan dosing schedule—the original dose approved by the FDA—involves taking two 400mg capsules every eight hours. If this dose is used, Crixivan should be taken on an empty stomach, meaning that you should not eat within two hours before or one hour after taking Crixivan. Alternatively, three-times-daily Crixivan can be taken with a light snack that does not contain fat (e.g., butter or milk).
- The more commonly used twice-daily Crixivan dosing schedule involves taking two 400mg capsules every 12 hours in combination with low doses of Norvir (ritonavir), another protease inhibitor. Norvir increases the amount of many HIV/AIDS drugs in the bloodstream, including Crixivan. This has a few advantages: it reduces the number of times a day Crixivan needs to be taken and eliminates the need to take Crixivan on an empty stomach. Because of these advantages, many doctors prefer to prescribe twice-daily Crixivan/Norvir instead of three-times-daily Crixivan (without Norvir). If Crixivan is combined with Norvir, the dose is usually two 400mg Crixivan capsules plus one or two 100mg Norvir capsules, twice a day. This dosing schedule has not been approved by the FDA.
- There is no official Crixivan dose for use in children. The correct dose of Crixivan—once it is made official—will depend on the size of the child. The dose currently being explored in clinical trials is 500mg per square meter of body surface area, every eight hours. Children with small body surface areas may require lower doses of the drug. No liquid or powder formulation has been developed. To learn about treatment options for children, click here.
- Clinical trials have determined that Crixivan is safe and effective when combined with other drugs, most notably two nucleoside reverse transcriptase inhibitors (NRTIs). Clinical trials have also suggested that Crixivan, combined with Norvir, is an effective option for people who have failed a protease inhibitor-based drug regimen in the past.
- For HIV-positive adults beginning anti-HIV drug therapy for the first time, Crixivan is not recommended as a protease inhibitor option by the United States Department of Health and Human Services (DHHS) in its treatment guidelines. Used without Norvir, Crixivan's three-times-daily dosing and food/fluid requirements are considered to be inconvenient. Used with Norvir, there is a high risk of kidney stones. Because of these issues, HIV-positive people starting treatment for the first time are encouraged to consider "preferred" or "alternative" protease inhibitor options (e.g., Norvir-boosted Reyataz, Norvir-boosted Lexiva, or Kaletra). To learn more about these recommendations and options, click here.
- If your viral load becomes detectable while taking a drug regimen that contains Crixivan, your doctor can order a drug-resistance test to see which drugs your virus are becoming less sensitive to. If your doctor finds that your virus is becoming resistant to Crixivan, it might be possible to begin taking a low dose of Norvir to boost the amount of Crixivan in the bloodstream. This can help overcome low-level resistance to Crixivan and help push viral load back down to undetectable levels.
- Many of the currently available protease inhibitors are affected by cross-resistance. This means that, if you've tried and failed a drug regimen in the past that contained a protease inhibitor, your virus might be resistant to Crixivan. Similarly, if you take an anti-HIV drug regimen that contains Crixivan and your virus becomes resistant to the drug, your virus might also be resistant to many of the other protease inhibitors available. This is why it is very important to use drug-resistance testing to determine which drugs your virus is no longer responding to if you experience a rebound in your viral load while taking an anti-HIV drug regimen. Often, a Norvir-boosted protease inhibitor, such as Kaletra (which contains lopinavir and Norvir in a single capsule) or Invirase (saquinavir) combined with Norvir, will be effective against strains of HIV that have become resistance to Crixivan. Also, new protease inhibitors that are active against HIV strains resistant to current protease inhibitors are being developed.
What about drug interactions?
- Crixivan is broken down (metabolized) by the liver, like many medications used to treat HIV and AIDS. This means that Crixivan can interact with other medications. Crixivan can lower or raise the levels of other medications in the body. Similarly, other medications can lower or raise the levels of Crixivan in the body. While many interactions are not a problem, some can cause your medications to be less effective or increase the risk of side effects.
- Tell your doctors and pharmacists about all medicines you take. This includes those you buy over-the-counter and herbal or natural remedies, such as St. John’s Wort. Bring all your medicines when you see a doctor, or make a list of their names, how much you take, and how often you take them. Your doctor can then tell you if you need to change the dosages of any of your medications.
- The following medications should not be taken while you are being treated with Crixivan:
Acid reflux/heartburn medications: Propulsid (cisapride)
Antimigraine medications: Methergine, Methylergometrine (methylergonovine); Ergostat, Cafergot, Ercaf, Wigraine (ergotamine); Ergotrate, Methergine (ergonovine); or D.H.E. 45, Migranal (dihydroergotamine)
Cholesterol-lowering drugs (statins): Zocor (simvastatin) and Mevacor (lovastatin)
Heart medications: Cordarone (amiodarone)
Antipsychotics: Orap (pimozide)
Sedatives: Versed (midazolam) and Halcion (triazolam)
Pulmonary Hypertension: sildenafil, used as Revatio
Herbal products: St. John's wort
- If Crixivan is combined with low-dose Norvir, the following medications should also be avoided:
Antifungals: Vfend (voriconazole)
Antihistamines: Hismanal (astemizole) or Seldane (terfenadine)
Heart medications: Vascor (bepridil), Tambocor (flecainide), Rythmol (propafenone), or Quinaglute/Quinidex (quinidine)
Enlarged prostate: Uroxatral (alfuzosin)
- Anticonvulsants, such as Tegretol ( carbamazepine), Luminal (phenobarbital), and Dilantin (phenytoin), decrease the amount of Crixivan in the bloodstream. Alternatives to these three anticonvulsants should be considered.
- Anti-HIV protease inhibitors can interact with Crixivan. Norvir (ritonavir) increases Crixivan levels in the bloodstream (the usual dose is 800mg plus 100mg or 200mg Norvir, twice a day). Kaletra (lopinavir/ritonavir) also increases Crixivan levels (the recommended dose is 600mg Crixivan plus the standard dose of Kaletra, twice a day). Crixivan can increase blood levels of Invirase (saquinavir); Invirase does not impact Crixivan levels (no dosing recommendation has been made). Crixivan can increase Viracept (nelfinavir) levels and Viracept can increase Crixivan levels (no dosing recommendation has been made). Crixivan also increases Agenerase (amprenavir)—and probably Lexiva (fosamprenavir)—levels in the bloodstream (changes in doses do not appear to be necessary). Reyataz (atazanavir) should not be combined with Crixivan because both drugs can cause increased bilirubin levels.
- Anti-HIV non-nucleoside reverse transcriptase inhibitors (NNRTIs) can also interact with Crixivan. Sustiva (efavirenz) and Viramune (nevirapine) can decrease Crixivan levels in the bloodstream. If either of these drugs are combined with Crixivan, the Crixivan dose should be increased to 1000mg three-times daily. However, if low doses of Norvir (ritonavir) are also being used to "boost" Crixivan, the Crixivan dose should be 800mg twice a day. Rescriptor (delavirdine) increases Crixivan levels in the bloodstream (the Crixivan dose should be reduced to 600mg three times a day and the Rescriptor dose should remain the same).
- It is also important to be careful when using the nucleotide reverse transcriptase inhibitor (NRTI) Videx (ddI) buffered tablets (not Videx EC capsules) with Crixivan. Videx buffered tablets can interfere with the absorption of Crixivan into the bloodstream. Because of this, the Videx buffered tablets must be taken either one hour before or one hour after taking Crixivan. It is okay to take Videx EC capsules and Crixivan at the same time.
- Crixivan can interact with some medications used to treat TB, MAC and other bacterial infections. Rifadin (rifampin) decreases Crixivan levels in the bloodstream; these two drugs should not be used together. Crixivan can increase Mycobutin (rifabutin) levels and Mycobutin decreases Crixivan levels (the Mycobutin dose should be reduced to 150mg daily or 300 mg three times a week). Crixivan can increase Biaxin (clarithromycin) levels in the bloodstream (the Biaxin dose does not need to be changed).
- Crixivan can interact with some medications used to treat thrush (candidiasis) and other fungal infections. Crixivan can increase Nizoral (ketoconazole) levels in the bloodstream. Because of this, the dose of Crixivan needs to be lowered while taking Nizoral, from 800mg three-times-daily to 600mg three-times-daily.
- Crixivan can increase the blood levels of oral contraceptives/birth-control pills. No changes in dosing have been recommended.
- Crixivan can increase blood levels of cochicine, which is used to treat gout. Lower doses of colchicine are recommended, and the two drugs should not be used together in people with liver or kidney impairment.
- Crixivan can increase blood levels of Advair, Flovent, or Flonase (fluticasone), the inhalable medications that are used to treat allergies and asthma. Alternatives to these drugs should be considered, especially for long-term use. Crixivan can also increase blood levels of an asthma medication called Serevent (salmeterol), a drug that is used to open the air passages in the lungs during an asthma attack. This can result in heart rhythm problems. Use of the two drugs together is not recommended.
- Crixivan can increase the blood levels of UroXatral (alfuzosin), a drug used to treat enlarged prostate glands. Increased alfuzosin blood levels can increase the risk of high blood pressure.
- Cholesterol-lowering drugs, also known as "statins," can interact with Crixivan. There are two statins that should not be used with Crixivan: Zocor (simvastatin) and Mevacor (lovastatin). Levels of these two drugs can become significantly increased in the bloodstream if they are combined with Crixivan, which increases the risk of side effects. The two statins that are considered to be the safest in combination with Crixivan are Pravachol (pravastatin) and Lescol (fluvastatin). It is also possible to take Crixivan with Lipitor (atorvastatin), although Crixivan can increase Lipitor levels in the bloodstream. If Lipitor is prescribed, it's best to begin treatment with the lowest possible dose of the drug and then increase the dose if necessary. Little is known about the newest statin, Crestor (rosuvastatin), although it is not expected to have any serious drug interactions with Crixivan or the other protease inhibitors.
- There is a class of drugs, known as PDE-5 inhibitors that are used to treat both erectile dysfunction and pulmonary arterial hypertension. Their brand names differ, depending on their use. Prezista/Norvir can significantly increase blood levels of these drugs.
When used to treat erectile dysfunction, it is best to use a lower dose of Viagra (sildenafil), Levitra (vardenafil) and Cialis (tadalafil) in order to reduce the risk of side effects. When used to treat pulmonary arterial hypertension, the dose of tadalafil (Adcirca) must be reduced if combined with Prezista/Norvir. Revatio (sildenafil) and Prezista/Norvir should not be used together.
- Herbal products can also interact with Crixivan. St. John's wort should not be used with Crixivan, since it can greatly reduce the amount of Crixivan in the bloodstream. HIV-positive people should also be cautious about using garlic supplements or milk thistle with Crixivan—test tube studies suggest that both herbal products can interact with the same liver enzyme system (cytochrome P450 3A4) responsible for metabolizing Crixivan. This may alter the amount of Crixivan in the bloodstream. These and other herbal products should be used with caution, until further studies are conducted.
- A number of other negative drug interactions are possible if Crixivan is combined with Norvir (ritonavir). To learn more about these drug interactions, click here.
What about side effects?
- Crixivan forms crystals in the urine, which occurs in as many as 40% of people taking this drug. This can cause kidney stones (nephrolithiasis), pain when urinating, and back pain. To reduce the risk of these side effects, it is advised that people taking Crixivan drink at least six eight-ounce glasses of water a day (at least 48 ounces).
- Some side effects of Crixivan involve the skin. People taking Crixivan are more likely to experience rash, dry skin, patches of dark skin (hyperpigmentation), hair loss, dry lips, and brittle fingernails and toenails.
- Crixivan can cause creatinine levels to increase in the bloodstream. Creatinine is a marker of muscle function. Increased creatinine levels, caused by Crixivan use, is not believed to be dangerous.
- Crixivan can cause bilirubin levels in the bloodstream to increase. Bilirubin is the waste product that results from the breakdown of hemoglobin molecules from worn out red blood cells. Crixivan can block the liver's removal of bilirubin from the bloodstream, which can cause bilirubin levels to become elevated and lead to jaundice (yellowing of the skin, eyes, and under the nails). Crixivan should not be combined with Reyataz (atazanavir), another protease inhibitor that can cause increased bilirubin levels.
- Anti-HIV drug regimens containing protease inhibitors, including Crixivan, can cause increased fat levels (cholesterol and triglycerides) in the blood, abnormal body-shape changes (lipodystrophy; including increased fat around the abdomen, breasts, and back of the neck, as well as decreased fat in the face, arms, and legs), and diabetes. These side effects of anti-HIV drug therapy are reviewed in our lessons on Lipodystrophy, Facial Lipoatrophy, and Risks To Your Heart (Hyperlipidemia).
- Short-term side effects include appetite loss, headaches, feeling crummy (malaise), diarrhea, nausea, and vomiting. Very often, these side effects improve within a few months/weeks of starting Crixivan.
Can pregnant women take Crixivan?
- Crixivan is classified by the FDA as a pregnancy category C drug. Pregnancy category C means that animal studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks. When taken during pregnancy, Crixivan levels in the bloodstream can become lower than normal, which can lead to drug resistance.Therefore, federal guidelines on the treatment of HIV-positive pregnant women recommend that low dose Norvir (ritonavir) be used to boost blood levels of Crixivan. HIV-positive women who become pregnant should discuss the benefits and possible side effects of anti-HIV treatment to help protect their babies from HIV (see our lesson called Family Planning, Pregnancy & HIV).
- It is not known whether Crixivan passes into breast milk and what effects it may have on a nursing baby. However, to prevent HIV transmission of the virus to uninfected babies, it is recommended that HIV-positive mothers not breast-feed.
Who should not take Crixivan?
- Before taking this medication, tell your doctor if you have kidney disease or liver disease. You may not be able to take Crixivan, or you may require a dosage adjustment or special monitoring during treatment if you have any of these conditions.
Where can I learn more about clinical trials that are using Crixivan?
- If you would like to find out if you are eligible for any clinical trials that include Crixivan, visit ClinicalTrials.gov, a site run by the U.S. National Institutes of Health. The site has information about all HIV-related clinical studies in the United States. For more info, you can call their toll-free number at 1-800-HIV-0440 (1-800-448-0440) or email firstname.lastname@example.org.