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Some fruit juices and fruits can interact with numerous drugs, in many cases causing adverse effects. The effect was first discovered accidentally, when a test of drug interactions with alcohol used grapefruit juice to hide the taste of the ethanol.

The effect is most studied with grapefruit and grapefruit juice, but similar effects have been observed with certain other citrus fruits. One medical review advises patients to avoid all citrus juices until further research clarifies the risks. Effects have been observed with apple juice, but their clinical significance is not yet known.

One whole grapefruit, or a small glass (200 mL (6.8 US fl oz)) of grapefruit juice, can cause drug overdose toxicity. Fruit consumed three days before the medicine can still have an effect. The relative risks of different types of citrus fruit have not been systematically studied. Affected drugs typically have an auxiliary label saying “Do not take with grapefruit” on the container, and the interaction is elaborated upon in the package insert. People are also advised to ask their physician or pharmacist about drug interactions.

The effects are caused by furanocoumarins (and, to a lesser extent, flavonoids). These chemicals inhibit key drug metabolizing enzymes, such as cytochrome P450 3A4 (CYP3A4). CYP3A4 is a metabolizing enzyme for almost 50% of drugs, and is found in the liver and small intestinal epithelial cells. As a result, many drugs are affected. Inhibition of enzymes can have two different effects, depending on whether the drug is either

1. metabolized by the enzyme to an inactive metabolite, or
2. activated by the enzyme to an active metabolite.

In the first instance, inhibition of drug-metabolizing enzymes results in elevated concentrations of an active drug in the body, which may cause adverse effects. Conversely, if the medication is a prodrug, it needs to be metabolised to be converted to the active drug. Compromising its metabolism lowers concentrations of the active drug, reducing its therapeutic effect, and risking therapeutic failure.

Low drug concentrations can also be caused when the fruit suppresses drug absorption from the intestine.

Modafinil, sold under the brand name Provigil among others, is a medication to treat sleepiness due to narcolepsy, shift work sleep disorder, or obstructive sleep apnea. While it has seen off-label use as a purported cognitive enhancer, the research on its effectiveness for this use is not conclusive. It is taken by mouth.

Common side effects include headache, anxiety, trouble sleeping, and nausea. Serious side effects may include allergic reactions such as anaphylaxis, Stevens–Johnson syndrome, misuse, and hallucinations. It is unclear if use during pregnancy is safe. The amount of medication used may need to be adjusted in those with kidney or liver problems. It is not recommended in those with an arrhythmia, significant hypertension, or left ventricular hypertrophy. How it works is not entirely clear. One possibility is that it may affect the areas of the brain involved with the sleep cycle.

Modafinil was approved for medical use in the United States in 1998. In the United States it is classified as a schedule IV controlled substance. In the United Kingdom it is a prescription only medication. It is available as a generic medication. In the United Kingdom it costs the NHS about £105.21 a month as of 2018. In the United States the wholesale cost per month is about US$34.20 as of 2018. In 2016, it was the 284th most prescribed medication in the United States, with more than a million prescriptions.

Sofosbuvir, sold under the brand name Sovaldi among others, is a medication used to treat hepatitis C. It is only recommended with some combination of ribavirin, peginterferon-alfa, simeprevir, ledipasvir, daclatasvir, or velpatasvir. Cure rates are 30 to 97% depending on the type of hepatitis C virus involved. Safety during pregnancy is unclear; some of the medications used in combination may result in harm to the baby. It is taken by mouth.

Common side effects include feeling tired, headache, nausea, and trouble sleeping. Side effects are generally more common in interferon-containing regimens. Sofosbuvir may reactivate hepatitis B in those who have been previously infected. In combination with ledipasvir, daclatasvir or simeprevir it is not recommended with amiodarone due to the risk of an abnormally slow heartbeat. Sofosbuvir is in the nucleotide analog family of medication and works by blocking the hepatitis C NS5B protein.

Sofosbuvir was discovered in 2007, and approved for medical use in the United States in 2013. It is on the World Health Organization's List of Essential Medicines, the safest and most effective medicines needed in a health system. As of 2016, a 12-week course of treatment costs about US$84,000 in the United States, US$53,000 in the United Kingdom, US$45,000 in Canada, and about US$500 in India. Over 60,000 people were treated with sofosbuvir in its first 30 weeks being sold in the United States.

Zoopharmacognosy is a behaviour in which non-human animals apparently self-medicate by selecting and ingesting or topically applying plants, soils, insects, and psychoactive drugs to prevent or reduce the harmful effects of pathogens and toxins. The term derives from Greek roots zoo ("animal"), pharmacon ("drug, medicine"), and gnosy ("knowing").

An example of zoopharmacognosy occurs when dogs eat grass to induce vomiting. However, the behaviour is more diverse than this. Animals ingest or apply non-foods such as clay, charcoal and even toxic plants and invertebrates, apparently to prevent parasitic infestation or poisoning.

Whether animals truly self-medicate remains a somewhat controversial subject because early evidence is mostly circumstantial or anecdotal, however, more recent examinations have adopted an experimental, hypothesis-driven approach.

The methods by which animals self-medicate vary, but can be classified according to function as prophylactic (preventative, before infection or poisoning) or therapeutic (after infection, to combat the pathogen or poisoning). The behaviour is believed to have widespread adaptive significance.