Tadalafil

Tadalafil is a PDE5 inhibitor marketed in pill form for treating erectile dysfunction (ED) under the name Cialis . and under the name Adcirca for the treatment of pulmonary arterial hypertension. In October 2011 the U.S. Food and Drug Administration (FDA) approved Cialis for treating the signs and symptoms of benign prostatic hyperplasia (BPH) as well as a combination of BPH and erectile dysfunction (ED) when the conditions coincide. It initially was developed by the biotechnology company ICOS. and then again developed and marketed world-wide by Lilly ICOS, LLC, the joint venture of ICOS Corporation and Eli Lilly and Company. Cialis tablets, in 2.5 mg, 5 mg, 10 mg, and 20 mg doses, are yellow, film-coated, and almond-shaped. The approved dose for pulmonary arterial hypertension is 40 mg (two 20-mg tablets) once daily.

Tadalafil is also manufactured and sold under the name of Tadacip by the Indian pharmaceutical company Cipla in doses of 10 mg and 20 mg.

On November 21, 2003 the FDA approved tadalafil (as Cialis) for sale in the United States as the third ED prescription drug pill (after sildenafil citrate (Viagra) and vardenafil Hydrochloride (Levitra)). Like sildenafil and vardenafil, tadalafil is recommended as an 'as needed' medication. Cialis is the only one of the three that is also offered as a once-daily medication.

Moreover, tadalafil was approved in May 2009 in the United States for the treatment of pulmonary arterial hypertension [1] and is under regulatory review in other regions for this condition. In late November 2008, Eli Lilly sold the exclusive rights to commercialize tadalafil for pulmonary arterial hypertension in the United States to United Therapeutics for an upfront payment of $150 million.

Contents

Tadalafil has been used in approximately 15,000 men participating in clinical trials, and over eight million men worldwide (primarily in the post-approval/post-marketing setting). The most common side effects when using tadalafil are headache, stomach discomfort or pain, indigestion, burping, acid reflux, back pain, muscle aches, flushing. and stuffy or runny nose. These side effects reflect the ability of PDE5 inhibition to cause vasodilation (cause blood vessels to widen), and usually go away after a few hours. Back pain and muscle aches can occur 12 to 24 hours after taking the drug, and the symptom usually disappears after 48 hours.

In May 2005, the U.S. Food and Drug Administration found that tadalafil (along with other PDE5 inhibitors) was associated with vision impairment related to NAION (nonarteritic anterior ischemic optic neuropathy ) in certain patients taking these drugs in the post-marketing (outside of clinical trials) setting. Most, but not all, of these patients had underlying anatomic or vascular risk factors for development of NAION unrelated to PDE5 use, including: low cup to disc ratio ("crowded disc"), age over 50, diabetes, hypertension, coronary artery disease, hyperlipidemia and smoking. Given the small number of NAION events with PDE5 use (fewer than one in one million), the large number of users of PDE5 inhibitors (millions) and the fact that this event occurs in a similar population to those who do not take these medicines, the FDA concluded that they were not able to draw a cause and effect relationship, given these patients underlying vascular risk factors or anatomical defects. However, the label of all three PDE5 inhibitors was changed to alert clinicians to a possible association.

In October 2007, the FDA announced that the labeling for all PDE5 inhibitors, including tadalafil, requires a more prominent warning of the potential risk of sudden hearing loss as the result of postmarketing reports of deafness associated with use of PDE5 inhibitors. [2]

Since PDE5 inhibitors such as tadalafil may cause transiently low blood pressure (hypotension ), organic nitrates (poppers) should not be taken for at least 48 hours after taking the last dose of tadalafil. Using organic nitrites (such as the sex drug amyl nitrite ) within this timeframe may increase the risk of life-threatening hypotension.

Since people who have taken tadalafil within the past 48 hours cannot take organic nitrates to relieve angina (such as glyceryl trinitrate spray), these patients should seek immediate medical attention if they experience anginal chest pain. [3] In the event of a medical emergency, paramedics and medical personnel should be notified of any recent doses of tadalafil.

Tadalafil is metabolized predominantly by the hepatic CYP3A4 enzyme system. The presence of other drugs which induce this system can shorten tadalafil half-life and reduce serum levels, and hence efficacy, of the drug.

Although sildenafil (Viagra), vardenafil (Levitra), and tadalafil (Cialis) all work by inhibiting PDE5, tadalafil's pharmacologic distinction is its longer half-life (17.50 hours) [4] – compared to sildenafil and vardenafil (both 4.0–5.0 hours) [5] – resulting in longer duration of action, and so partly responsible for "The Weekend Pill" sobriquet. Furthermore, the longer half-life is the basis for current investigation of tadalafil's daily therapeutic use in relieving pulmonary arterial hypertension. Sildenafil is approved in several world regions as a thrice-daily therapy for pulmonary arterial hypertension.

Penile erection during sexual stimulation is caused by increased penile blood flow resulting from the relaxation of penile arteries and the smooth muscle of the corpus cavernosum. This response is mediated by the release of nitric oxide (NO) from nerve terminals and endothelial cells, which stimulates the synthesis of Cyclic guanosine monophosphate (more commonly known as Cyclic GMP or cGMP) in smooth muscle cells. cGMP relaxes smooth muscle and increases blood flow to the corpus cavernosum.

The inhibition of phosphodiesterase type 5 (PDE5) enhances erectile function by increasing the amount of cGMP. Tadalafil (and sildenafil and vardenafil) inhibits PDE5. However, because sexual stimulation is required to initiate the local penile release of nitric oxide, tadalafil's inhibition of PDE5 will have no effect without direct sexual stimulation of the penis. The recommended tadalafil starting dose for most men is 10 mg, taken as needed before sexual activity (but not more than once daily). The dose may be increased to 20 mg or decreased to 5 mg, per its efficacy and the man's personal tolerance of the drug. In June 2007, the European Commission approved low-dose (2.5 mg and 5 mg) Cialis to be used as single-daily ED therapy.

Although available since 2003 in 5, 10, 20 mg dosage, in late 2008/early 2009, the U.S. FDA approved the commercial sale of Cialis in 2.5 mg dosage as a one-a-day treatment for ED. The 2.5 mg dose avoids earlier dispensing restrictions on higher dosages. The price of the 5 mg and 2.5 mg are often similar, so some people score and split the pill. [6] Both physicians and the manufacturer warn against splitting the pill, especially since it is enterically coated and splitting might impact absorption.

Moreover, tadalafil (Adcirca) 40 mg was approved in 2009 in the United States and Europe (and 2010 in Canada and Japan) as a once-daily therapy to improve exercise ability in patients with pulmonary arterial hypertension. In patients with pulmonary arterial hypertension. the pulmonary vascular lumen is decreased as a result of vasoconstriction and vascular remodeling, resulting in increased pulmonary artery pressure and pulmonary vascular resistance. Tadalafil is believed to increase pulmonary artery vasodilation, and inhibit vascular remodeling, thus lowering pulmonary arterial pressure and pulmonary vascular resistance. Right heart failure is the principal consequence of pulmonary arterial hypertension.

On October 6, 2011, the U.S. FDA approved tadalafil to treat the signs and symptoms of benign prostatic hyperplasia (BPH). BPH is a condition in males in which the prostate gland becomes enlarged, obstructing the free flow of urine. Symptoms may include sudden urges to urinate (urgency), difficulty in starting urination (hesitancy), a weak urine stream, and more frequent urination - especially at night. The FDA has also approved tadalafil for treatment of both BPH and erectile dysfunction (ED) where the two conditions co-exist.

Selectivity compared with other PDE5 inhibitors Edit

Tadalafil, sildenafil, and vardenafil all act by inhibiting the PDE5 enzyme. These drugs also inhibit other PDE enzymes. Sildenafil and vardenafil inhibit PDE6, an enzyme found in the eye, more than tadalafil. [7] Some sildenafil users see a bluish tinge and have a heightened sensitivity to light because of PDE6 inhibition. [8] Sildenafil and vardenafil also inhibit PDE1 more than tadalafil. [7] PDE1 is found in the brain, heart, and vascular smooth muscle. [7] It is thought that the inhibition of PDE1 by sildenafil and vardenafil leads to vasodilation. flushing. and tachycardia. [7] Tadalafil inhibits PDE11 more than sildenafil or vardenafil. [7] PDE11 is expressed in skeletal muscle. the prostate. the liver. the kidney. the pituitary gland. and the testes. [7] The effects on the body of inhibiting PDE11 are not known. [7]

The FDA's approval of sildenafil on March 27, 1998 [10] was a ground-breaking commercial event for the treatment of ED, with sales exceeding US$ 1 billion. Subsequently, the FDA approved Levitra (vardenafil ) on August 19, 2003, [11] and Cialis (tadalafil) on November 21, 2003.

Cialis was discovered by Glaxo Wellcome (now GlaxoSmithKline ) under a partnership between Glaxo and ICOS to develop new drugs that began in August 1991. [12] [13] In 1993, the Bothell, Washington biotechnology company ICOS Corporation began studying compound IC351, a phosphodiesterase type 5 (PDE5) enzyme inhibitor. In 1994, Pfizer scientists discovered that sildenafil, which also inhibits the PDE5 enzyme, caused penile erection in men participating in a clinical study of a heart medicine. Although ICOS scientists were not testing compound IC351 for treating ED, they recognized its potential usefulness for treating that disorder. Soon, in 1994, ICOS received a patent for compound IC351 (structurally unlike sildenafil and vardenafil), and Phase 1 clinical trials began in 1995. In 1997, the Phase 2 clinical studies were initiated for men experiencing ED, then progressed to the Phase 3 trials that supported the drug's FDA approval. Although Glaxo had an agreement with ICOS to share profits 50/50 for drugs resulting from the partnership, Glaxo let the agreement lapse in 1996 as the drugs developed were not in the company's core markets. [8]

In 1998, ICOS Corporation and Eli Lilly and Company formed the Lilly ICOS, LLC, joint venture company to further develop and commercialize tadalafil as a treatment for ED. Two years later, Lilly ICOS, LLC, filed a new drug application with the FDA for compound IC351 (under the tadalafil generic name, and the Cialis brand name). In May 2002, Lilly ICOS reported to the American Urological Association that clinical trial testing demonstrated that tadalafil was effective for up to 36 hours, and one year later, the FDA approved tadalafil. One advantage Cialis has over Viagra and Levitra is its 17.5-hour half-life (thus Cialis is advertised to work for up to 36 hours, [14] after which time there remains approximately 25 percent of the absorbed dose in the body) when compared to the four-hour half–life of sildenafil (Viagra).

In 2007, Eli Lilly and Company bought the ICOS Corporation for $2.3 billion. As a result, Eli Lilly owned Cialis and then closed the ICOS operations, ending the joint venture and firing most of ICOS's approximately 500 employees, except for 127 employees of the ICOS biologics facility, which subsequently was bought by CMC Biopharmaceuticals A/S (CMC).

Persons surnamed "Cialis" objected to Eli Lilly and Company's so naming the drug, but the company has maintained that the drug's trade name is unrelated to the surname. [15]

On October 6, 2011, the U.S. FDA approved tadalafil [16] to treat the signs and symptoms of benign prostatic hyperplasia (BPH). BPH is a condition in males in which the prostate gland becomes enlarged, obstructing the free flow of urine. Symptoms may include sudden urges to urinate (urgency), difficulty in starting urination (hesitancy), a weak urine stream, and more frequent urination- especially at night. The FDA has also approved tadalafil for treatment of both BPH and erectile dysfunction (ED) where the two conditions co-exist.

Marketing Edit

20 mg Cialis tablet

In the United States, the FDA relaxed rules on prescription drug marketing in 1997, allowing advertisements targeted directly to consumers. [17] Lilly-ICOS hired the Grey Worldwide Agency in New York, part of the Grey Global Group. to run the Cialis advertising campaign. [18] Marketers for Cialis has taken advantage of its greater duration compared to its competitors in advertisements for the drug; Stuart Elliot of The New York Times opined: "The continuous presence of women in Cialis ads is a subtle signal that the drug makes it easier for them to set the pace with their men, in contrast to the primarily male-driven imagery for Levitra and Viagra." [18] Iconic themes in Cialis ads include couples in bathtubs and the slogan "When the moment is right, will you be ready?" [18] Cialis ads were unique among the ED drugs in mentioning specifics of the drug. [19] As a result, Cialis ads were also the first to describe the side effects in an advertisement, as the FDA requires advertisements with specifics to mention side effects. One of the first Cialis ads aired at the 2004 Super Bowl. [19] Just weeks before the Super Bowl, the FDA required more possible side effects to be listed in the advertisement, including priapism. [19] Although many parents objected to the Cialis ad being aired during the Super Bowl, Janet Jackson 's halftime "wardrobe malfunction " overshadowed Cialis. [19] In January 2006, the Cialis ads were tweaked, adding a doctor on screen to describe side effects and only running ads where more than 90 percent of the audience are adults, effectively ending Super Bowl ads. [17] In 2004, Lilly-ICOS, Pfizer, and GlaxoSmithKline spent a combined $373.1 million to advertise Cialis, Viagra, and Levitra respectively. [19] Cialis has sponsored many sporting events, including the America's Cup and the PGA Tour. once being title sponsor of the PGA Tour Western Open tournament. [20]

In the United States as of 2015 the cost is between 29.84 and 45.83 USD per 10mg pill. [21]

What is Cialis (tadalafil)?

Cialis (tadalafil) relaxes muscles and increases blood flow to particular areas of the body.
Cialis (tadalafil) is used to treat erectile dysfunction (impotence).
Cialis (tadalafil) may also be used for purposes other than those listed in this medication guide.

What should I discuss with my doctor before taking Cialis (tadalafil)?

Do not take Cialis (tadalafil) if you are also using a nitrate drug for chest pain or heart problems. This includes nitroglycerin (Nitrostat, Nitrolingual, Nitro-Dur, Nitro-Bid, and others), isosorbide dinitrate (Dilatrate-SR, Isordil, Sorbitrate), and isosorbide mononitrate (Imdur, ISMO, Monoket). Nitrates are also found in some recreational drugs such as amyl nitrate or nitrite ("poppers"). Taking tadalafil with a nitrate medicine can cause a serious decrease in blood pressure, leading to fainting, stroke, or heart attack.

A small number of patients have had a sudden loss of eyesight after taking tadalafil. This type of vision loss is caused by decreased blood flow to the optic nerve of the eye. It is not clear whether tadalafil is the actual cause of such vision loss. Sudden vision loss with tadalafil use has occurred most often in people with heart disease, diabetes, high blood pressure, high cholesterol, or certain pre-existing eye problems, and in those who smoke or are over 50 years old.

Before taking Cialis (tadalafil), tell your doctor if you have:
heart disease or heart rhythm problems;
a recent history of heart attack (within the past 90 days);
a recent history of stroke or congestive heart failure (within the past 6 months);
angina (chest pain);
high or low blood pressure;
liver disease;
kidney disease (or if you are on dialysis);
a blood cell disorder such as sickle cell anemia, multiple myeloma, or leukemia;
a bleeding disorder such as hemophilia;
a stomach ulcer;
retinitis pigmentosa (an inherited condition of the eye);
a physical deformity of the penis (such as Peyronie's disease); or
if you have been told you should not have sexual intercourse for health reasons.

If you have any of these conditions, you may not be able to use tadalafil or you may need a dosage adjustment or special tests during treatment.

FDA pregnancy category B: Although tadalafil is not for use in women, this medication is not expected to be harmful to an unborn baby. Do not use tadalafil without telling your doctor if you are pregnant or plan to become pregnant during treatment.
Although Cialis (tadalafil) is not for use in women, it is not known if tadalafil passes into breast milk or if it could harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.
You may need a lower dose of this medication if you are older than 65. Follow your doctor's instructions.

How should I take Cialis (tadalafil)?

Take each dose with a full glass of water.
Avoid taking High-fat food before taking Viagra as it may cause the medicine to take more time to start working.
Tadalafil is usually taken only when needed, 30 - 60 minutes before sexual activity. The medication can help achieve an erection when sexual stimulation occurs. An erection will not occur just by taking a pill.
Do not take tadalafil more than once a day. Allow 24 hours to pass between doses.
Store this medication at room temperature away from moisture and heat.

What happens if I miss a dose?

Since tadalafil is used as needed, you are not likely to be on a dosing schedule.

What happens if I overdose?

Seek emergency medical attention if you think you have used too much of this medicine.
Symptoms of a tadalafil overdose may include chest pain, nausea, irregular heartbeat, and feeling light-headed or fainting.

What should I avoid while taking tadalafil?

Avoid drinking alcohol, which can increase some of the side effects of tadalafil.
Grapefruit and grapefruit juice may interact with tadalafil. Discuss the use of grapefruit products with your doctor. Do not increase or decrease the amount of grapefruit products in your diet without first talking to your doctor.
Do not use any other drug to treat impotence, such as alprostadil (Caverject, Muse, Edex) or yohimbine (Yocon, Yodoxin, others), unless your doctor tells you to.

What are the possible side effects of tadalafil?

If you become dizzy or nauseated, or have pain, numbness, or tingling in your chest, arms, neck, or jaw during sexual activity, stop and call your doctor right away. You could be having a serious side effect of tadalafil.
Stop using tadalafil and get emergency medical help if you have sudden vision loss.
Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.
Stop using tadalafil and call your doctor at once if you have any of these serious side effects:
chest pain or heavy feeling, pain spreading to the arm or shoulder, nausea, sweating, general ill feeling;
irregular heartbeat;
swelling in your hands, ankles, or feet;
shortness of breath;
vision changes;
feeling light-headed, fainting; or
penis erection that is painful or lasts 4 hours or longer.
Continue taking tadalafil and talk with your doctor if you have any of these less serious side effects:
warmth or redness in your face, neck, or chest;
stuffy nose;
headache;
upset stomach; or
back pain.
Side effects other than those listed here may also occur. Talk to your doctor about any side effect that seems unusual or that is especially bothersome.
What drug(s) may interact with Cialis (tadalafil)?

Do not take tadalafil if you are taking the following medications:
nitroglycerin-type drugs for the heart or chest pain such as amyl nitrite, isosorbide dinitrate, isosorbide mononitrate, nitroglycerin, even if these are only taken occasionally

Cialis (tadalafil) may also interact with the following medications:
alpha blockers, such as alfuzosin (UroXatral), doxazosin (Cardura), prazosin (Minipress), or terazosin (Hytrin), used to treat high blood pressure or an enlarged prostate.
bosentan
certain antibiotics such as clarithromycin, erythromycin, troleandomycin
certain drugs used for seizures such as carbamazepine, phenytoin, and phenobarbital
cimetidine
cisapride
diltiazem
grapefruit juice
medicines for fungal infections (fluconazole, itraconazole, ketoconazole, voriconazole)
mibefradil
nicardipine
certain medicines for the treatment of HIV infection or AIDS
quinidine
rifabutin, rifampin or rifapentine
some drugs for treating depression, anxiety or other mood problems (examples: fluoxetine, fluvoxamine, nefazodone)
verapamil

What is Cialis (tadalafil)?

Cialis (tadalafil) relaxes muscles and increases blood flow to particular areas of the body.
Cialis (tadalafil) is used to treat erectile dysfunction (impotence).
Cialis (tadalafil) may also be used for purposes other than those listed in this medication guide.

What should I discuss with my doctor before taking Cialis (tadalafil)?

Do not take Cialis (tadalafil) if you are also using a nitrate drug for chest pain or heart problems. This includes nitroglycerin (Nitrostat, Nitrolingual, Nitro-Dur, Nitro-Bid, and others), isosorbide dinitrate (Dilatrate-SR, Isordil, Sorbitrate), and isosorbide mononitrate (Imdur, ISMO, Monoket). Nitrates are also found in some recreational drugs such as amyl nitrate or nitrite ("poppers"). Taking tadalafil with a nitrate medicine can cause a serious decrease in blood pressure, leading to fainting, stroke, or heart attack.

A small number of patients have had a sudden loss of eyesight after taking tadalafil. This type of vision loss is caused by decreased blood flow to the optic nerve of the eye. It is not clear whether tadalafil is the actual cause of such vision loss. Sudden vision loss with tadalafil use has occurred most often in people with heart disease, diabetes, high blood pressure, high cholesterol, or certain pre-existing eye problems, and in those who smoke or are over 50 years old.

Before taking Cialis (tadalafil), tell your doctor if you have:
heart disease or heart rhythm problems;
a recent history of heart attack (within the past 90 days);
a recent history of stroke or congestive heart failure (within the past 6 months);
angina (chest pain);
high or low blood pressure;
liver disease;
kidney disease (or if you are on dialysis);
a blood cell disorder such as sickle cell anemia, multiple myeloma, or leukemia;
a bleeding disorder such as hemophilia;
a stomach ulcer;
retinitis pigmentosa (an inherited condition of the eye);
a physical deformity of the penis (such as Peyronie's disease); or
if you have been told you should not have sexual intercourse for health reasons.

If you have any of these conditions, you may not be able to use tadalafil or you may need a dosage adjustment or special tests during treatment.

FDA pregnancy category B: Although tadalafil is not for use in women, this medication is not expected to be harmful to an unborn baby. Do not use tadalafil without telling your doctor if you are pregnant or plan to become pregnant during treatment.
Although Cialis (tadalafil) is not for use in women, it is not known if tadalafil passes into breast milk or if it could harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.
You may need a lower dose of this medication if you are older than 65. Follow your doctor's instructions.

How should I take Cialis (tadalafil)?

Take each dose with a full glass of water.
Avoid taking High-fat food before taking Viagra as it may cause the medicine to take more time to start working.
Tadalafil is usually taken only when needed, 30 - 60 minutes before sexual activity. The medication can help achieve an erection when sexual stimulation occurs. An erection will not occur just by taking a pill.
Do not take tadalafil more than once a day. Allow 24 hours to pass between doses.
Store this medication at room temperature away from moisture and heat.

What happens if I miss a dose?

Since tadalafil is used as needed, you are not likely to be on a dosing schedule.

What happens if I overdose?

Seek emergency medical attention if you think you have used too much of this medicine.
Symptoms of a tadalafil overdose may include chest pain, nausea, irregular heartbeat, and feeling light-headed or fainting.

What should I avoid while taking tadalafil?

Avoid drinking alcohol, which can increase some of the side effects of tadalafil.
Grapefruit and grapefruit juice may interact with tadalafil. Discuss the use of grapefruit products with your doctor. Do not increase or decrease the amount of grapefruit products in your diet without first talking to your doctor.
Do not use any other drug to treat impotence, such as alprostadil (Caverject, Muse, Edex) or yohimbine (Yocon, Yodoxin, others), unless your doctor tells you to.

What are the possible side effects of tadalafil?

If you become dizzy or nauseated, or have pain, numbness, or tingling in your chest, arms, neck, or jaw during sexual activity, stop and call your doctor right away. You could be having a serious side effect of tadalafil.
Stop using tadalafil and get emergency medical help if you have sudden vision loss.
Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.
Stop using tadalafil and call your doctor at once if you have any of these serious side effects:
chest pain or heavy feeling, pain spreading to the arm or shoulder, nausea, sweating, general ill feeling;
irregular heartbeat;
swelling in your hands, ankles, or feet;
shortness of breath;
vision changes;
feeling light-headed, fainting; or
penis erection that is painful or lasts 4 hours or longer.
Continue taking tadalafil and talk with your doctor if you have any of these less serious side effects:
warmth or redness in your face, neck, or chest;
stuffy nose;
headache;
upset stomach; or
back pain.
Side effects other than those listed here may also occur. Talk to your doctor about any side effect that seems unusual or that is especially bothersome.
What drug(s) may interact with Cialis (tadalafil)?

Do not take tadalafil if you are taking the following medications:
nitroglycerin-type drugs for the heart or chest pain such as amyl nitrite, isosorbide dinitrate, isosorbide mononitrate, nitroglycerin, even if these are only taken occasionally

Cialis (tadalafil) may also interact with the following medications:
alpha blockers, such as alfuzosin (UroXatral), doxazosin (Cardura), prazosin (Minipress), or terazosin (Hytrin), used to treat high blood pressure or an enlarged prostate.
bosentan
certain antibiotics such as clarithromycin, erythromycin, troleandomycin
certain drugs used for seizures such as carbamazepine, phenytoin, and phenobarbital
cimetidine
cisapride
diltiazem
grapefruit juice
medicines for fungal infections (fluconazole, itraconazole, ketoconazole, voriconazole)
mibefradil
nicardipine
certain medicines for the treatment of HIV infection or AIDS
quinidine
rifabutin, rifampin or rifapentine
some drugs for treating depression, anxiety or other mood problems (examples: fluoxetine, fluvoxamine, nefazodone)
verapamil