Modafinil Combinations – Full Guide 2022

Modafinil Combinations

Modafinil is a eugeroic medication used for the treatment of excessive sleep disorders. But unlike other eugeroics, it is a non-stimulant with less dependence potential. Online Modafinil in Australia works on the neurotransmitters to produce wakefulness and alertness. Increasing the dopamine levels shakes off the grogginess and lethargy caused by excessive sleepiness and keeps the patient alert and awake for stipulated time intervals. Because of its cognitive efficiency, it is used offhand by people from various fields, including students, entrepreneurs, gamers, and sportspersons, for increased mental stimulation and improved work efficiency. However, when used with certain foods, drinks, or drugs, it can lead to a drug interaction.

A Word about Drug and Food Interactions

A drug interaction is a change in the action of a medication when used concomitantly or in combination with other foods, supplements, or medications. A drug interaction can occur when two drugs combined lead to a change in their pharmacodynamics i.e., additive or diminished effects. It can also occur through pharmacokinetic interaction through differences in the absorption, transport, metabolism and excretion of the compounds. Either way, drug interactions can lead to several side effects ranging from mild symptoms of decreased metabolism to severe reactions like serotonin syndrome and myocardial infarction.

Modafinil Combinations

Modafinil Combinations can be divided into:-

– Medicine Combinations

– Food and Drinks combination

Medicine Combinations

Modafinil with Antidepressants

SSRI, Tricyclic antidepressants, MAOIs and NaSSAs, are the types of antidepressants most commonly used for the treatment of depression and anxiety disorders. Of these categories, there are a few antidepressants that cause moderate to severe adverse reactions when combined with Modafinil. Tranylcypromine, Isocarboxazid and Phenelzine, and Selegiline are a few such medicines.

Tranylcypromine (Brand name Parnate), and Isocarboxazid (brand name Marplan) are MOIs that regulate the balance of certain neurotransmitters in the brain to help in the treatment of depression. Combining them with Modafinil results in pharmacodynamic synergism leading to increased levels of Modafinil. This, in turn, results in overdosing symptoms like acute hypertension with increased pulse rate and other complications. Selegiline (brand name Eldepryl) and Phenelzine are a few other MAOIs that concomitant use with Modafinil leads to serious overdosing symptoms.

Tricyclic antidepressants like Amoxapine, Imipramine, Desipramine, and Nortriptyline when combined together with Modafinil may lead to adverse reactions like dry mouth, sedation, blurred vision and constipation. In rare cases, it may even lead to urinary retention.

When concomitantly used with Modafinil, SSRIs like Citalopram and Escitalopram can lead to life-threatening situations like irregular heart rhythm. Other problems like lightheadedness, fainting, and shortness of breath have also been known to occur when Modafinil is consumed along with SSRIs.

Modafinil with Cobimetinib and other Anticancer Drugs

Studies have proved that Modafinil can be used for reducing fatigue in patients receiving chemotherapy for cancer treatment. But its concomitant use in a few anticancer medications can lead to adverse reactions. Cobimetinib is one such example. Cobimetinib is an antineoplastic agent and MEK (Mitogen-activated extracellular Kinase) used in the treatment of melanoma. When used in combination with Modafinil, it affects the CYP3A4 enzyme and decreases the level and effectiveness of Cobimetinib in the body. This, in turn, reduces its effectiveness in cancer treatment.

Avapritinib, Axitinib, Abemaciclib, Brigatinib, and Acalabrutinib are other anticancer medications when combined with Modafinil, leading to decreased effectiveness. While Avapritinib is used to treat gastrointestinal tumors, Axitinib is a chemotherapy medication used for cases of renal cancer. Brigatinib and Abemaciclib are used in lung and breast cancer, respectively. Their associated use should be avoided for the safety of the patient.

Modafinil with HIV Medications

NRTIs, NNRTIs, protease inhibitors, fusion inhibitors, CCR5 antagonists, and attachment with post-attachment inhibitors are some common classes of HIV medications.

Tenofovir (brand names Vemlidy, Viread) is an NRTI used to treat HIV, and Hepatitis B. Combined use with Modafinil may reduce Tenofovir levels from the system leading to reduced effectiveness of the drug. Even Truvada, Atripla, and Complera, the combination medications of Tenofovir and Emtricitabine, show reduced effectiveness when combined with Modafinil.

When combined with Triumeq (a combination of two NRTIs), it decreases the medication’s plasma concentrations, resulting in its quicker elimination from the body. This results in reduced effectiveness of the medication with gastric discomfort resulting due to its unnatural elimination.

With protease inhibitors like Atazanavir, Norvir (Ritonavir), and Amprenavir, the plasma concentrations of Modafinil may increase, leading to its accumulation in the bloodstream.

Modafinil with Antibiotics and Anti-Parasitic Drugs

Usually, Modafinil does not interact with antibiotics and can be safely taken together with most of them. Ciprofloxacin and Linezolid are a few exceptions.

Ciprofloxacin and Bedaquiline, an anti-tuberculosis medication in combination with Modafinil, can lead to increased plasma concentrations of Modafinil with a decrease in its own plasma concentrations. It results in a decrease in their effectiveness with overdose of Modafinil in the patient’s system.

Linezolid is another antibiotic that reacts inversely with Modafinil. Linezolid is used in the treatment of infections caused by gram-positive bacteria. A combination of these two can increase the concentration of Modafinil in the system with an increased risk of high blood pressure or acute hypertensive episode. Similar effects have been observed on combining Lefamulin, an antibiotic for lung infections, with Modafinil.

Anti-parasitic medications like Albendazole and Ivermectin and antifungals like Brexafemme show a decrease in their plasma concentrations and subsequently reduced effectiveness when consumed along with Modafinil.

Modafinil with Adderall and Ritalin

Adderall and Ritalin are both CNS active medications used to treat ADHD (Attention Deficit Hyperactivity Disorder). Ritalin is a CNS stimulant that, apart from ADHD, is used in a variety of mood, sleep, and body disorders. Adderall is a combination medication that comes in handy for treating Narcolepsy and as a cognitive enhancer. Modafinil, also being a stimulant, when combined with Adderall or Ritalin, leads to overstimulation with an increased risk of side effects. Research has proved that combining these medications delays the absorption of Modafinil as well. Vyvanse (Lisdexamfetamine) is another ADHD medication whose use is contraindicated alongside Modafinil.

Modafinil with Anticoagulants

Anticoagulants are medications used in the treatment of blood clots either through delay or prevention methods. Studies have proved that some of these medications should not be used with the concomitant use of Modafinil. Aspirin and Modafinil do not cause any serious adverse reactions. But the risk of excessive bleeding is increased by combining Warfarin and Anisindione with Modafinil. Apixaban and Betrixaban are a few other anticoagulants whose plasma concentration is decreased on coadministration with Modafinil. This results in their reduced effectiveness that can cause life-threatening problems for the patient.

Modafinil with Antiepileptic Medications

Antiepileptic medications are used to treat and prevent seizures either through decreased excitation or enhanced inhibition method. When used concomitantly with Modafinil, some of these medications show decreased effectiveness tendencies on either side. Amobarbital and Aminoglutethimide, like Elipten, are a few such drugs. The effectiveness of Modafinil is reduced on their combined use. Brivaracetam on Modafinil combination leads to an increased plasma concentration of the former in the bloodstream. This can result in overdosing symptoms leading to emergencies.

Modafinil with Beta-Blockers and CAD Medications

Beta Blockers and other CAD medications are used to treat a variety of heart-related disorders in people. These medications as such should be used carefully as any improper use may lead to fatal problems.

Though not all beta-blockers, the use of propranolol with Modafinil may lead to its increased effects with subsequently increased blood pressure. Amlodipine is a calcium channel blocker used to treat angina and high blood pressure, while Amiodarone is used against ventricular arrhythmia. Ambrisentan (brand name Cialis) is used in the treatment of pulmonary arterial hypertension. All of these drugs have been known to show decreased effectiveness when coadministered with Modafinil. Similar effects have been observed with Atorvastatin, a statin used in cholesterol treatment, and Amiodarone- used for ventricular arrhythmia. Arformoterol combination with Modafinil can cause serious side effects like irregular heart rhythm and elevated heart rate.

Modafinil with Benzodiazepines and Barbiturates

Benzodiazepines are a group of medications with anxiolytic, sedative, and myorelaxant properties. They are used for anxiety disorders, insomnia, and even seizures in patients. Barbiturates are medications with sleep-inducing and anxiety-reducing properties. These medications like Modafinil work on the neurotransmitters of CNS to bring out their therapeutic effects. Combining these two at the same time leads to disruption in the properties of either medication.

Alprazolam (Xanax) and Diazepam (Valium) are two important Benzos that interact differently when combined with Modafinil. Stacking Modafinil with Xanax decreases its effectiveness, while combining Modafinil with Diazepam increases its levels in the bloodstream leading to overdosing effects. It is important to remember that the level of interaction varies from person to person. While stacking Modafinil with Benzos may affect some people adversely, the combination may benefit others. It depends on the severity of the condition and the tolerance level of the patient. Likewise, Butabarbital and Butalbital are barbiturates that decrease the effectiveness of Modafinil on combined use. Care should be taken on avoiding their concomitant use for the safety of the patient

Modafinil with Painkillers and Opioid Analgesics

Analgesics are used in a variety of conditions to achieve symptomatic relief from pain. Opioid analgesics are medications in the analgesic group that works on the opioid receptors for pain-relieving properties. Because of their similar binding mechanism in the CNS, analgesics like Amlotriptan and Modafinil adversely interact with each other. Opioid analgesics like Alfentanil and chronic pain medications like Buprenorphine, Methadone, Oxycodone, and Hydrocodone decrease in effectiveness when combined with Modafinil.

Modafinil with Anti-inflammatory Drugs

Contrary to analgesics, which reduce pain by blocking pain signaling to the brain, anti-inflammatory drugs actually reduce inflammation and provide symptomatic relief to the patient. Both steroidal and non-steroidal anti-inflammatory drugs like Betamethasone and Apremilast have been known to show reduced effectiveness when combined with Modafinil. Dexamethasone, another prominent anti-inflammatory medication, reduces the effectiveness of Modafinil when used together. Contrary to these anti-inflammatory drugs, Aspirin and Diclofenac show no such interactions and can be safely used together.

Modafinil with Antihistamines and COPD Medications

Antihistamines, medications used in treating allergic conditions, while COPD, are useful for a variety of lung disorders. Astemizole, a second-generation Antihistamine used for allergic rhinitis and urticaria, reduces its effectiveness with Modafinil. Hydroxyzine, another antihistamine, has shown mixed interaction with Modafinil and thus is contradicted for concomitant use.

COPD medications like Albuterol and Terbutaline increase irregular heart rhythm with increased blood pressure when combined with Modafinil. Kidney medication like Finerenone also produces similar results on its concomitant use with Modafinil.

Food Interactions of Modafinil

Modafinil with Coffee

Both Modafinil and Coffee are Nootropics, i.e., agents that provide mental stimulation without addictive potential. While Modafinil is a prescription nootropic, coffee or caffeine is a natural nootropic that works on the brain receptors for awakening and alertness effects.

Mixing Modafinil with coffee can be helpful to the patient and improve his cognitive capacity. A 50-100 mg Modafinil with one cup of coffee is considered an ideal dose. More than 200 mg is considered as excess and can cause overdosing symptoms with an increase in the risk of side effects. Some users have reported irregular heartbeat, shakiness, and confusion as well. Additionally, coffee and Modafinil both increase Norepinephrine production, and combining the two can make you sleep faster with improved sleep quality. The best way to combine Modafinil with coffee is to consume coffee 1-2 hours after Modafinil and sip it very slowly to avoid any overstimulation symptoms.

Modafinil with Grapefruit and Alcohol

When combined with grapefruit, Modafinil leads to side effects in the form of nausea, vomiting, sleeplessness, etc. Modafinil and alcohol have polar opposite mechanisms of action. At the same time, Modafinil is a stimulant and stimulates neurotransmitters; alcohol works as a depressant and attacks these neurotransmitters. Combining them can reduce the effectiveness of Modafinil and should be avoided as such for the safety of the patient.

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